How to diagnose and treat mild cognitive impairment from Alzheimer's disease?

With the advent of an aging society, Alzheimer's disease (AD) imposes a heavy social and economic burden on the global public health syst.
A series of pathophysiological changes may occur in brain tissue more than 20 years before typical symptoms of AD appe.
During this process, mild cognitive impairment (MCI), namely AD-derived MCI, is the earliest stage with clinical sympto.
This stage becomes the most important window for early detection, diagnosis and prevention of .
In order to meet the needs of clinical practice and further improve the awareness of the majority of medical workers on AD-derived MCI, experts from the Dementia and Cognitive Impairment Group of the Neurology Branch of the Chinese Medical Association have formulated this "Alzheimer's Pathogeny" after many discussio.
Chinese Expert Consensus on Diagnosis and Treatment of Mild Cognitive Impairment, with a view to providing consensus and guidance for the early diagnosis, early intervention and precise treatment of .
MCI classification MCI is usually divided into two subtypes: amnestic MCI (aMCI) and non-amnestic MCI (naMC.
aMCI mainly manifests as obvious memory impairment; while naMCI mainly manifests as other cognitive impairments, such as impairment of attention, language, visuospatial function or executive functi.
aMCI is likely to progress to AD, but it is not completely equivalent to AD-derived MCI, and naMCI may progress to other types of dementia, such as vascular dementia, frontotemporal dementia, e.
(Figure
 Figure 1 Epidemiology of mild cognitive impairment (MCI) classification of AD-derived MCI ➤ Recommendations: (1) The incidence of MCI in China is similar to other countries in the wor.
The epidemiological investigation of sexual MCI and the diagnostic criteria for AD-derived MCI after epidemiological investigation are provided for use (IIa recommendation, level of evidence .
(2) In the epidemiological investigation, attention should be paid to the unified diagnostic criteria, and the authoritative scales, biological markers and other inspection methods should be used as much as possible to improve the diagnostic accuracy (expert consensu.
 The etiology and pathological mechanism of AD-derived MCI AD is a continuous disease spectrum, including preclinical AD, AD-derived MCI, mild AD, moderate AD and severe .
Its main pathological feature is the deposition of Aβ to form nerve cells Inflammatory plaques, neurofibrillary tangles (NFTs) formed by abnormal phosphorylation of tau protein, neuronal loss and gliosis,e.
The long preclinical stage of AD occurs 10 to 20 years before clinical sympto.
At this time, Aβ has begun to gradually deposit in the precuneus and cerebral cortex, followed by hypometabolism, tau pathology, and reduced hippocampal volume in these regio.

for cognitive impairme.

 The etiological hypotheses of AD-derived MCI mainly include the following:Amyloid hypothesisTau hyperphosphorylation hypothesisPrion-like transmission hypothesisInteraction between Aβ and cerebrovascular abnormalitiesNeuroinflammation hypothesis ➤ Recommendations: (1) AD is a chronic and complex disease involving a variety of pathophysiological chang.

The pathogenesis hypotheses are diversifi.

It is necessary to re-examine the pathogenesis of AD, and systematically demonstrate the relationship between different mechanism hypotheses from a holistic vi.

Searching for effective control targets for AD-derived MCI (expert consensu.

 (2) According to the possible etiology and pathophysiological changes of AD, the main characteristics of biomarkers in MCI stage are determined, which can be used to observe the evolution of the disease during the disease-modifying treatment of AD-derived MCI (expert consensu.

 Main clinical manifestations of AD-derived MCI ➤ Recommendations: (1) Perform instrumental daily ability or social function tests for all MCI patients (level I recommendation, level A evidenc.

(2) Pay attention to the characteristics of cognitive impairment in MCI patients and the characteristics of transformation to AD (expert consensu.

(3) Attention should be paid to the evaluation of suspected MCI and NPS performance of MCI patients, and to guide diagnosis and treatment to improve the quality of life of patients (Class I recommendation, Level A evidenc.
 Diagnosis and differential diagnosis of AD-derived MCI ➤ The clinical diagnostic criteria for MCI include the following 4 points: (1) Cognitive impairment reported by patients or insiders, or found by experienced clinicians; (2) The presence of one or more cognitive impairments Objective evidence of domain impairment (neuropsychological tests), of which episodic memory impairment is the most common; (3) complex instrumental daily activities can be slightly impaired, but independent activities of daily living are maintained; (4) diagnostic criteria for dementia have not been m.

 The diagnosis of AD-derived MCI was first proposed in the AD diagnostic guidelines issued by the NIA-AA working group in 2011, that is, the detection of AD-related markers was added to the clinical diagnostic criteria of MCI (see the section on body fluid examination and imaging examination for detail.

 ➤The diagnosis of MCI follows the following procedures: (1) According to the patient's cognitive function and daily living ability (confirmed by neuropsychological tests), the diagnosis of MCI is made according to the MCI diagnostic criter.

(2) In the case of MCI, based on the cognitive assessment results, the patients are initially classified according to the cognitive domain of impairment; if the diagnosis of MCI is not yet satisfied, follow-up is recommended, and reconfirmation is performed after 6 months or when there is a significant change in cognitive functi.

functional che.

(3) Combining the onset and development of MCI, the characteristics of cognitive impairment, the presence or absence of primary neurological diseases (or stress events) or the history and signs of systemic diseases, and necessary auxiliary examinations, make the etiology of MCI diagnos.

For patients with MCI for the first time, it is recommended to follow up for at least 1 year to further confirm the diagnos.

 ➤The diagnosis and differential diagnosis of AD-derived MCI is divided into five parts: history collection, physical examination, neuropsychological assessment, body fluid examination and imaging examinati.

Collection of medical history While inquiring about patients, necessary information should also be obtained from their family members or inside.
Collection content: onset time, onset form, specific manifestations, progression, diagnosis and treatment process and outcome; whether cognitive impairment has an impact on daily ability and social function; whether accompanied by NPS, specific manifestations of NPS, and cognitive impairment The sequence of occurrence of the disorder; possible predisposing factors or events of cognitive impairment; accompanying abnormal limb function or symptoms and signs of other systemic diseas.

 MCI caused by neurodegenerative diseases has an insidious onset and continuous progression, generally without a known disease causing cognitive impairment, often without focal neurological signs or selectively involving a certain syst.

It is necessary to ask in detail about family history, tumor history (to check for paraneoplastic syndrome), blood transfusion and travel history (syphilis or HIV infection), and collection of past medical history, especially if there are diseases or predisposing factors that cause cognitive impairment, such as brain Vascular disease, Parkinson's disease and Parkinson's-plus syndrome, normal pressure hydrocephalus, traumatic brain injury, encephalitis, epilepsy, chronic diarrhea or malnutrition (vitamin B1 or B12 deficiency), thyroid dysfunction, liver and kidney insufficiency , alcoholism, carbon monoxide poisoning, substance abuse, vascular risk factors (such as hypertension and diabetes), depression, sleep-disordered breathing,e.

 Second, physical examination Including general physical examination and neurological examinati.

Nervous system examinations include consciousness, advanced cortical function tests (comprehension, orientation, far and near memory, calculation and judgment, e.

), cranial nerves, motor system (muscle volume, muscle tone, muscle strength, involuntary movement, mutual aid, Gait), sensory system (superficial, deep, complex), reflex (superficial, deep, pathological), and meningeal irritation sig.

The neurological signs associated with MCI of different etiologies are different, and the physical examination needs to be tailored to individual conditio.

Neuropsychological assessment Neuropsychological assessment helps to establish the diagnosis of MCI through the evaluation of the patient's cognitive function, daily and social activities, and NPS; it can clarify the characteristics of the patient's cognitive impairment for further classification and etiological diagnosis; changes in cognitive abilities can be monitor.
 ➤Recommendation: (1) The neuropsychological assessment of AD-derived MCI needs to include: a comprehensive assessment of cognitive function, daily and social abilities, and NPS (expert consensu.

(2) Assessment of neurocognitive function in AD-derived MCI, MoCA and/or modified ACE-III are recommended as screening scales; the main cognitive function areas are assessed including: memory, executive function, language, visuospatial and structure Aspects of competence (expert consensu.

(3) Episodic memory impairment is an important basis for the diagnosis and differential diagnosis of AD-derived M.

The California word learning test, the Chinese version of the Hopkins word learning test, and delayed free cue recall can be select.

For executive function assessment, it is recommended to choose connection test and digital sign conversion test; for language ability assessment, Boston naming test, semantic fluency test, and Chinese aphasia test can be select.

Visual space and structure ability assessment can choose Rey-Osterricth complex figure test, clock drawing test and so .

Computerized assessment of cognitive function may be an option for the assessment of AD-derived MCI (expert consensu.

(4) For the diagnosis of MCI in highly educated individuals, periodic neuropsychological scale testing and longitudinal follow-up comparisons are recommended to detect their cognitive decline and the process of transformation to AD (expert consensu.

Body fluid examination ➤Recommendation: (1) Plasma Aβ42/Aβ40, P-tau217, P-tau181 and NfL can be used for early diagnosis of AD-derived MCI and assessment of disease progression (Class IIa recommendation, Level A evidenc.

(2) Cerebrospinal fluid Aβ42, Aβ42/Aβ40, P-tau181, P-tau217, T-tau, and NfL can be used for early diagnosis of AD-derived MCI and assessment of disease progression (Class I recommendation, Level A evidenc.
(3) Cerebrospinal fluid testing is recommended in the following situations: patients with subjective cognitive decline (without impairment of cognitive ability according to objective tests); persistent, progressive and unexplained MCI; patients with symptoms suggestive of AD; age of onset of MCI Early (<65 years old); patients with behavioral changes as the main symptoms (such as paranoid delusions, unexplained delirium and depression) and the diagnosis of AD is considered (class I recommendation, level of evidence .

(4) MCI patients with a clear family history of dementia should undergo genetic testing to help diagnose (Class I recommendation, Level A evidenc.

(5) Genetic testing is suitable for individuals with a clear family history and an obvious risk of autosomal dominant inheritance (Class IIb recommendation, Level B evidenc.

(6) ApoE genotype detection can be used for risk stratification of MCI patients, predicting the risk of transformation to AD, and can be used for efficacy analysis in clinical research (Class IIa recommendation, Level B evidenc.

(7) Genetic diagnosis should be carried out in professional and qualified testing institutions to ensure the accuracy of testing (expert consensu.

.

Imaging examinations ➤ Recommendations: (1) The diagnostic criteria for AD-derived MCI are recommended to adopt NIA-AA diagnostic criteria (2011, 2018) and IWG-2 (2014), and pay attention to AD-related biological markers in the Application of diagnosis of AD-derived MCI (Class I recommendation, Level A evidenc.

(2) When pathological, humoral or molecular imaging (PET) marker detection cannot be carried out, other types of MCI (Parkinson's disease, vascular disease, Lewy body disease, autologous Immune encephalopathy and other related MCI), MCI patients with AD-derived MCI neuropsychological cognitive impairment features (such as hippocampal amnestic disorder syndrome) and head MRI imaging features, can diagnose "AD-derived MCI" from the clinical work level (Expert Consensu.
 Non-drug treatment and drug treatment of AD-derived MCINon-drug treatment ➤Recommendation: (1) Non-drug interventions are recommended for AD-derived MCI patients, including cognitive training, moderate-intensity physical exercise, and reasonable diet (such as Mediterranean diet) (Class IIa recommendation, Level B evidenc.

(2) rTMS treatment can help improve patients' overall cognitive function, episodic memory and language function (Class IIb recommendation, Level B evidenc.

(3) Computer-assisted cognitive training can be a beneficial supplement to AD-derived MCI intervention (Class I recommendation, Level A evidenc.

(4) Multimodal intervention consisting of diet, exercise, cognitive training and other means can improve or maintain the cognitive function of the elderly at high risk of AD, and help to delay the transformation of MCI to AD (Class IIa recommendation, A level of evidenc.

Drug treatment ➤ Recommendations: (1) The cholinesterase inhibitor donepezil can delay the progression of AD-derived MCI to AD in the early stage, but its long-term effect still needs more large-sample clinical trials to study (Class IIa recommendation, level of evidence .

(2) DMT with monoclonal antibodies against Aβ (such as aducanumab) is likely to be an effective treatment for AD-derived MCI (Class IIa recommendation, Level B evidenc.

(3) Drugs that reshape the balance of intestinal flora (such as sodium mannitol) can reduce peripheral-related amino acid metabolites, reduce brain neuroinflammation, and improve cognitive function, which may improve AD-derived MCI (Class IIb recommendation, Level B evidenc.

(4) EGb761, a Ginkgo biloba extract, improves cognitive function in AD, but its role in AD-derived MCI still needs to be studied in large-scale clinical trials (Class IIb recommendation, Level B evidenc.

(5) Patients with AD-derived MCI need to pay attention to emotional disorders (anxiety, depression, e.

) and deal with them in time, which may benefit in reducing the risk of MCI to AD transformati.
Donepezil can delay the progression of AD-derived MCI with depression to AD (Class IIa recommendation, Level B evidenc.

(6) The use of donepezil may be beneficial for AD-derived MCI patients with abnormal gait and at risk of falling (Class IIa recommendation, Level B evidenc.

(7) When using antipsychotics to treat NPS in AD-derived MCI, the risk of cognitive decline must be weighed (expert consensu.

Suggestions for health care workers and caregivers ➤ Recommendations: (1) Health care workers should inform patients that: combined interventions, including comprehensive management of risk factors, cognitive training, exercise therapy and home care, social interaction therapy, for prevention or Delaying cognitive impairment is beneficial (expert consensu.

(2) Reasonable daily care, environmental improvement, and care for the caregivers are beneficial to improving the quality of life of patients and delaying the process of cognitive impairment (expert consensu.

Prognosis and Outcome ➤ Recommendations: (1) The risk of AD-derived MCI patients being transformed into AD is significantly increased, and early diagnosis should be paid attention to (Class I recommendation, Level A evidenc.

(2) AMCI patients with normal cognitive function still have the risk of transforming into AD, and need regular follow-up and evaluation (recommended follow-up evaluation every 3-6 months) (Class I recommendation, Level B evidenc.

(3) The application of biological markers (including body fluids and imaging) can more accurately assess the risk of AD-derived MCI patients transforming into AD (expert consensu.

 Prevention of AD-derived MCI Prevention of AD-derived MCI is divided into primary prevention and secondary preventi.

Primary prevention is to identify controllable risk factors for AD-derived MCI and reduce the risk to prevent the occurrence of MCI or the pathophysiological progression of AD-derived MCI; Intervention and prevention of MCI to AD conversion
 ➤Recommendation: (1) Reasonable diet, regular physical and mental exercise, good sleep, blood pressure control, prevention and treatment of diabetes, cerebrovascular disease, atrial fibrillation, e.

are helpful for the prevention of AD-derived M.

(Class I recommendation, Level B evidenc.

(2) There is currently no effective secondary preventive measures for AD-derived MCI (Class IIa recommendation, Level B evidenc.

 Yimaitong is compiled from: Dementia and Cognitive Impairment Group of Neurology Branch of Chinese Medical Associati.

Chinese Expert Consensus on Diagnosis and Treatment of Alzheimer's Disease-derived Mild Cognitive Impairment 202 Chinese Journal of Neurology, 2022, 55(5): 421 -44