Guide and standardize the treatment of vascular cognitive impairment

Vascular cognitive impairment (VCI) refers to the risk factors of cerebrovascular disease (primary hypertension, diabetes, hyperlipidemia and hyperhomocysteinemia, etc.
), dominant cerebrovascular disease (ischemia Syndromes ranging from mild cognitive impairment to dementia caused by non-dominant cerebrovascular diseases (leukopenia, chronic cerebral ischemia, etc.
)
.

VCI treatment aims to actively treat the cause, improve clinical symptoms, slow the progression of cognitive impairment, control complications, and improve the quality of life of patients
.

01

Cause treatment

Vascular risk factors and cerebrovascular disease are the initial link of VCI.
Early control of risk factors and treatment of cerebrovascular disease are the most fundamental measures for the treatment of VCI
.

02

Cognitive impairment treatment

1.
Cholinesterase inhibitor

VaD and AD overlap in neuropathology and neurochemistry.
About 30% of patients with post-stroke dementia or subcortical vascular dementia (SIVD) show the same pathological changes as AD
.

(1) Donepezil: Several international randomized, double-blind, placebo, and controlled studies have shown that donepezil can improve the cognitive function of VaD patients, as well as the overall function and ability of daily living of patients, and there is a dose-effect.
Relationship, 10 mg/d donepezil can improve the behavioral symptoms of VaD patients, and the effect is better than 5 mg/d
.

(2) Galantamine: Galantamine is a second-generation cholinesterase inhibitor, which can improve the cognitive function of VaD patients, especially executive function, and has a trend of improving overall cognitive function; another item Large-scale studies have shown that galantamine does not significantly improve the ADAS-Cog score of patients, but it can improve patients' cognitive function, psycho-behavioral symptoms and ability of daily living
.

(3) Rivastigmine: Whether rivastigmine is effective in the treatment of VaD, there is no clear conclusion yet
.

(4) Huperzine A: Huperzine A is an alkaloid isolated from the Huperzia plant Melaleuca.
It has a small molecular weight, high fat solubility, easier to penetrate the blood-brain barrier, and has a high oral organism.
Utilization can inhibit cholinesterase activity for a long time.
However, its efficacy on VaD has only been confirmed in small-scale clinical trials, and large-scale, multi-center, randomized controlled clinical trials are still needed to draw conclusions
.

2.
Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist

Memantine can improve the cognitive impairment and psycho-behavioral symptoms (BPSD) of patients with mild to moderate VaD, and improve the behavior and overall clinical impression of patients with severe VaD.
It has good safety and tolerability, but there are also studies suggesting it There is no obvious improvement effect on the overall clinical score/activity of daily living, and the efficacy is not clear
.

3.
Other drugs

(1) Butylphthalide: The clinical research of butylphthalide in the treatment of subcortical VCIND by domestic scholars found that butylphthalide can effectively improve the cognitive function and overall function of patients with ischemic subcortical VCIND, and has good safety.
And tolerance
.

(2) Nimodipine: A 52-week double-blind placebo-controlled trial failed to prove that nimodipine can improve the overall cognitive function and behavioral ability of SIVD patients, but the prognostic evaluation scale shows that the drug has an effect on executive function.
Certain improvement effect
.

(3) Nicergoline: Nicergoline may be effective for post-stroke cognitive impairment, but there are few clinical studies on the treatment of VaD, and the effective evidence for the treatment of VaD needs to be further supplemented
.

(4) Oxiracetam: Oxiracetam can improve the cognitive function and overall clinical impression of VaD patients to a certain extent, and it can also improve the overall function.
However, high-quality, large-scale clinical trials are still needed to draw conclusions
.

(5) Ginkgo preparation: It can improve the cognitive function of VaD patients, but it cannot improve the ability of daily living
.

4.
Chinese patent medicine

Traditional Chinese medicine has made remarkable progress in the treatment of VaD with the holistic concept and syndrome differentiation and treatment as its essence
.

03

Treatment of psycho-behavioral symptoms

The occurrence of BPSD has aggravated the functional impairment of patients and increased the burden of medical treatment and care.
It is a difficult point in the clinical treatment of VCI
.

1.
VCIND

The BPSD of VCIND patients is relatively rare and mild, and non-drug treatment should be preferred, including psychological counseling and counseling, adjustment of the surrounding environment, music therapy and behavioral therapy, etc.
, which can reduce the patient's BPSD
.

2.
VaD

VaD patients have more common BPSD, with more severe degrees, and various manifestations, including depression, anxiety, apathy, hallucinations, delusions, agitation, sleep inversion, impulsive and aggressive behaviors
.
If the symptoms make the patient painful or put the patient or others in danger, medication should be given, and the following principles should be followed
.

(1) Anti-dementia drugs, including cholinesterase inhibitors and NMDA receptor antagonists, are first used for the drug treatment of BPSD in VaD patients, which may improve the cognitive function impairment of VaD patients as well as their mental and behavioral symptoms
.

(2) When BPSD is further aggravated and cholinesterase inhibitors and NMDA receptor antagonists are not effective, short-term use of atypical antipsychotic drugs can be used
.
Olanzapine and risperidone can improve BPSD in patients with dementia, and aripiprazole can also improve BPSD in patients with dementia
.
However, it should be noted that atypical antipsychotics can increase the risk of cerebrovascular disease and death in patients, especially elderly patients
.
Therefore, for BPSD, anti-dementia drugs should be used first, and atypical antipsychotics should be used as second-line drugs in small doses and short-term.
Patients and their families should be clearly informed of the possible benefits and risks before medication
.
The reference dose is shown in Table 1
.
For the elderly (usually over 85 years old), you can choose 1/2 of the recommended dose in Table 1 as the starting dose
.
At the same time, it is necessary to evaluate the effects of the above drugs on other diseases of the patient, as well as drug interactions and contraindications
.

Table 1 The recommended starting and maintenance doses of commonly used antipsychotics for the treatment of BPSD

(3) VaD patients are often accompanied by mood disorders.
Patients with depression can be treated with selective serotonin reuptake inhibitors (SSRIs), but it should be noted that different SSRIs have different mechanisms of action
.
Citalopram and sertraline have little effect on P450 enzymes, less drug interactions, and better safety, but the QT interval should be monitored during the application of citalopram
.
VaD patients with depression often show anxiety at the same time.
SSRIs can improve anxiety as well as depression
.
SSRIs drugs are relatively safe.
Adverse reactions mainly include gastrointestinal symptoms, insomnia, agitation, tremor, akathisia, sexual dysfunction, etc.
The frequency and severity of adverse reactions of different SSRIs drugs may be different, and attention should be paid to individualization.
Medication, use with caution
.
For patients with good compliance, if the dose of antidepressant reaches the maximum effective dose tolerated by the individual or there is no obvious effect in sufficient dose for at least 4 weeks, the drug can be determined to be ineffective and consider changing the dressing (Class I recommendation, Level A evidence)
.
Dressing change is not limited to different types, but can also be performed between the same types (type I recommendation, level A evidence); if two similar antidepressants have been used, it is recommended to switch to a different type of drug treatment (type I) Recommendation, A-level evidence)
.
Patients with obvious physical symptoms such as anxiety and pain can choose antidepressants with corresponding therapeutic effects, such as venlafaxine, duloxetine, etc.
, may consider short-term low-dose combined use of benzodiazepine? Drugs and other anti-anxiety drugs
.
Benzodiazepine? Common adverse reactions of these drugs include sleepiness, dizziness, ataxia, memory impairment, respiratory depression, drug resistance, addiction, and drug withdrawal syndrome
.
Taking into account the cognitive impairment of VaD patients, therefore, the use of non-benzodiazepines? Class drugs are more suitable
.
Patients with obvious sleep disorders can also choose antidepressants with sedative and sleep-improving effects, such as mirtazapine and trazodone
.

In short, the treatment of VCI should follow the principle of early diagnosis and early treatment, comprehensive treatment for vascular risk factors, cerebrovascular disease, cognitive impairment and complications, etc.
, pay attention to adverse drug reactions and drug interactions, and regular follow-up and evaluation Adjust the treatment plan in time for the efficacy and adverse reactions of the drug
.