Yan Wenming, Department of Radiotherapy, Affiliated Hospital of Inner Mongolia Medical University
Sun Dongfeng, Yan Wenming (Reviewer)
Chinese Journal of Practical Medicine
[Keywords] Vascular dementia; vascular cognitive impairment; diagnosis; treatment outcome
【Category】R749.1
Vascular dementia (VaD) is the second cause of dementia in old age, accounting for 10%-50% of dementia [1].VaD is a syndrome, not a single disease, and different vascular pathological changes can cause VaD symptoms, including large and small arterial lesions, diffuse ischemic white matter lesions, embolization of heart dislodged emboli, hemodynamic changes, bleeding, hematological factors and hereditary diseases, etc [2].
Current diagnostic criteria for vascular dementia do not detect non-demented cognitive impairment and facilitate the prevention and treatment of vascular dementia. The concept of vascular cognitive impairment can be used to cover all degrees of cognitive impairment related to vascular risk factors and cerebrovascular lesions, facilitating early identification and early intervention [3].
1 Vascular dementia (VaD) and vascular cognitive impairment (VCI) [3]
Vascular dementia (VaD) is a distinct subcortical dementia with executive dysfunction. In recent years, with the establishment of cerebrovascular disease (CVD) as a direct or indirect risk factor for dementia. clinical diagnostic criteria for VaD have gradually been established. The most specific diagnostic criteria for VaD, DSM-IV, are currently used internationally, with three types of diagnosis: “probable”, “suspicious” and “definite”. The VaD diagnostic criteria of the National Institute of Neurological Disorders and the Swiss International Association for Neuroscience Research [4] have been widely accepted because of their high specificity and are now widely used in clinical trials for screening simple VaD cases. The various VaD diagnostic criteria emphasize the need for evidence of dementia and CVD (history, clinical presentation and neuroimaging evidence) and the existence of a correlation between the two (i.e., dementia occurring within a certain period of time after stroke), which has led to the diagnosis of VaD being divided into two steps: first, dementia is identified (meeting the definition of dementia using Alzheimer’sD isease,AD as template definition of dementia) and then differentiate it from AD (based on vascular risk factors, ischemic scores, imaging changes, etc.). Many clinical and neuropsychological studies have shown that following the diagnostic criteria for AD-type dementia does not allow for the detection of many cognitive impairments due to CVD, especially in those who do not meet the criteria for dementia, and does not allow for early detection and prevention. Therefore, after the 1990s, some scholars proposed that VaD should be represented by the broader concept of vascular cognitive impairment (VDI), with the aim of getting rid of the VaD diagnostic criteria from the traditional dementia criteria [5], and the patients identified by the currently applied VaD diagnostic criteria are all patients with advanced cognitive impairment that cannot be recovered, which cannot achieve early detection and early intervention. The social and medical significance of the concept lies in the fact that it is free from the traditional definition of dementia and emphasizes that cognitive impairment caused by vascular lesions can be diagnosed and intervened early to avoid the aggravation of damage to the extent that it affects the ability to perform occupational, social and daily life.
VCI is a group of diseases caused by multiple etiologies. Depending on the severity of the cognitive impairment, VCI can be classified into vascular amnestic cognitive impairment (MCI), vascular non-dementia cognitive impairment, and VaD. vascular non-dementia cognitive impairment is probably the most common type of VCI. It can be divided into cortical (macrovascular, embolic and hypoperfusion), critical site (macrovascular, embolic, small vessel and hypoperfusion) and subcortical (small vessel, hypoperfusion and incomplete infarct) according to the site of lesion; the diagnostic criteria for vascular non-dementia cognitive impairment are cognitive impairment that does not meet the diagnostic criteria for dementia and also has the basis of vascular lesion.
Diagnostic criteria for VCI: presence of cerebrovascular disease risk factors or cerebrovascular disease; fluctuating development of cognitive impairment; relatively preserved or less impaired memory and more impaired cognitive functions such as attention and executive; causal relationship between cerebrovascular disease and cognitive impairment, with the exception of other diseases; insufficient diagnostic criteria for dementia.
2 Classification of VaD [6, 7] and basic diagnostic elements
The neuropathological classification of VaD includes dementia due to ischemic and hemorrhagic brain damage, and hypoxic-hypoperfusion dementia.
The most essential elements for the diagnosis of VaD: (i) symptoms of dementia; (ii) history, clinical examination and brain imaging confirming the presence of cerebrovascular disease (CVD); and (iii) both must be correlated.
The diagnosis of dementia in ICD-10 [8] requires the presence of memory loss and mental retardation that affects the ability to perform daily activities. “CVD is defined as the presence of focal neurological signs consistent with stroke, with or without a history of stroke. The ischemic index (IS) is widely used to diagnose MID [9]. In addition to evidence of CVD, a clear correlation between stroke and dementia syndromes is required for the diagnosis of VaD. Sudden or stepwise cognitive impairment with concomitant CVD that can be confirmed by brain imaging should be considered as if the patient has had a stroke.
3 Use of brain imaging in the diagnosis of VaD
Although there are no characteristic brain CT or MRI findings that are diagnostic for VaD, the absence of CVD on CT or MRI essentially negates the diagnosis of VaD and is a strong basis for differentiating AD from VaD. As a basis for considering the diagnosis of VaD, brain imaging shows damage to local anatomical structures and severity that meets at least certain criteria [6, 10]. Although the relationship between the volume of brain damage and dementia is not certain, there may be a cumulative effect.
4 Diagnostic criteria for vascular dementia
VaD is a compound disease caused by ischemic stroke, hemorrhagic stroke, or ischemic-hypoxic brain damage. the NINDS-AIREN diagnosis of VaD [6] is divided into 3 levels of considerable (possible), probable (possible), and definite (definite), as follows.
4.1 Clinical diagnosis of probable (possible) VaD criteria, including the following items.
(1) Dementia. Decreased cognitive function compared to the past, as evidenced by memory impairment and impairment in two or more cognitive domains (orientation, attention, language, visual-spatial function, executive function, motor control, and executive function). It is best determined by clinical and neuropsychological testing. These functional deficits are sufficient to interfere with the patient’s daily life and are not solely caused by a somatic impairment due to stroke.
Exclusion criteria: cases with impaired consciousness, delirium, psychosis, severe aphasia, significant sensorimotor impairment without evidence of neuropsychological testing. And exclude other systemic diseases and other brain disorders that can cause memory and cognitive dysfunction.
(2) Cerebrovascular disease. Neurological examination with focal signs such as hemiparesis, lower facial palsy, Babinski’s sign, sensory loss, hemianopia, dysarthria, etc., consistent with stroke (with or without a history of stroke). Evidence of associated cerebrovascular disease on brain imaging (CT or MRI), including multiple large vessel strokes, or single significant intra-regional infarcts (angular gyrus, thalamus, basal forebrain, anterior cerebral artery, and posterior cerebral artery feeding areas), multiple basal ganglia and luminal lesions within the white matter, and extensive periventricular ischemic white matter damage, or both.
(3) The diagnosis of both of these diseases is correlated. At least 1 or more of the following: (1) Dementia manifestations occur 3 months after stroke; (2) There is sudden deterioration of cognitive function, or fluctuating, stage-progressive cognitive deficits.
4.2 Clinical features consistent with possible VaD are.
(1) early gait instability (minigait, ataxic gait, or Parkinsonian gait).
(2) The presence of unstable, frequent, unexplained falls.
(3) Early onset of urinary frequency, urgency, and other urinary tract symptoms that cannot be explained by urologic disease.
(4) Pseudobulbar palsy.
(5) Personality changes, emotional apathy, depression, emotional incontinence, other subcortical deficit symptoms such as psychomotor retardation and executive function abnormalities.
4.3 The features that exclude the diagnosis of VaD are.
(1) early manifestations of memory deficits that progressively worsen with other cognitive impairments such as impairments in language (transcortical sensory aphasia), motor skills (disuse), and perception (dyscognition), and the absence of associated focal impairments on brain imaging.
(2) No focal neurological signs other than cognitive impairment.
(3) No vascular lesions on CT or MRI of the brain.
4.4 Considerable (Possible) VaD.
Presence of dementia with focal neurological signs but no CVD findings on brain imaging; or lack of a clear transient association between dementia and stroke; or presence of CVD but slow onset and inconsistent disease course characteristics (no plateau or improvement period).
4.5 Definite diagnostic criteria for VaD.
(1) Clinically consistent with probable (probably) VaD.
(2) Histopathological examination (biopsy or autopsy) confirming VaD.
(3) Absence of neurofibrillary tangles and senile plaques beyond the age-limited number.
(4) Absence of other clinical and pathological conditions that cause dementia.
Classification of VaD for research purposes can be made on the basis of clinical conditions, radiological findings and neuropathology, such as thalamic dementia classified as cortical VaD and subcortical VaD.
5 Advances in the treatment of vascular dementia and cognitive impairment [3]
To date, the treatment of VaD is still divided into two categories: prophylactic and symptomatic treatment. Prophylactic treatment focuses on the control of vascular risk factors, i.e. primary and secondary prevention of stroke. Symptomatic treatment involves various pharmacodynamic mechanisms, including cholinesterase inhibitors (ChEI), neurotrophic and neuroprotective drugs, N-methyl-D-aspartate receptor antagonists NMDA, antioxidants, microcirculation improvement, puzzling drugs, hormone replacement therapy, and anti-inflammatory therapy. From the perspective of evidence-based medicine, the current therapeutic agents with the highest level of evidence are ChEI and NMDA receptor antagonists.
ChEI have been approved for the treatment of AD, including donepezil, carboplatin, galantamine and tacrine, due to their clear improvement in cognition and overall function in patients with mild to moderate AD. Donepezil, a hexahydropyridine derivative, is a centrally reversible ChEI, and clinical studies have concluded that a 6-month treatment with donepezil improves cognitive function, overall function, and activities of daily living in patients with mild to moderate VaD, but the therapeutic effect in patients with severe disease remains to be seen [11]. Galantamine has the dual effect of increasing cholinergic neurotransmission by inhibiting cholinesterase and modulating central nicotinic receptors. Clinical studies of likely VaD patients treated with galantamine maintained or received the same degree of improvement in cognitive function and activities of daily living after 12 months [12]. Carboplatin is a dual inhibitor of butyryl esterase and acetylcholinesterase. Prefrontal dysfunction as manifested by poor executive function and behavioral abnormalities is prominent in patients with subcortical VaD, and the efficacy of carbaratine in this subtype suggests that it may target the prefrontal lobes [13]. Propofol inhibits neuronal adenosine reuptake, inhibits CAMP catabolic enzymes, and may have neuroprotective effects by inhibiting overactive microglia and reducing oxygen free radical levels. Nimodipine is a dihydropyridine calcium channel blocker, which has a certain effect on cerebrovascular autoregulation, can dilate cerebral blood vessels, block L-type calcium channels and have certain neuroprotective effects, and is particularly effective in small vessel disease. Memantine is a new low to moderate affinity, voltage-dependent, non-competitive NMDA receptor antagonist with specific pharmacogenetic characteristics that allow it to reduce glutamate toxicity and have neuroprotective effects without affecting the physiological role of glutamate receptors in learning and memory, and has been approved as a treatment for moderate to severe AD in Europe and the United States in 2002 and 2003, respectively [14].
Although research with VaD treatment is still active, to date, no drug has been approved for the treatment of VaD. Continuing the search for more effective treatments for VaD, such as AChEI in combination with memantine, other puzzling or neuroprotective drugs will likely be the next step in the research [15].
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