Vascular cognitive impairment (VCI) encompasses all types of cognitive symptoms caused by circulatory disturbances, irrespective of the exact mechanisms.
Information processing symptoms may manifest as narrow disturbances in one or more areas of cognitive function, or they may be progressive, extensive states that lead to severe memory disorder (old term: vascular dementia).
The key causes of VCI are small vessel disease (SVD) and large vessel disease (LVD). Other types include states caused by cerebral haemorrhages, hypoperfusion and hereditary causes.
The VCI group also contains mixed aetiologies where, in addition to a degenerative brain disease (most commonly Alzheimer's disease), also a clinically significant cerebrovascular disease has a role.
Epidemiology and risk factors
Symptoms involving memory, executive functioning, as well as functions involving perception and speech are common after strokes due to cerebral infarction or haemorrhage. Following a cerebrovascular disorder, impairment of cognitive functions occurs in at least half of all patients. In studies on the Finnish population, 41% of working-age patients and even up to 71% of elderly patients with cerebral infarction have been found to have clinically significant impairment of at least one area of cognitive function, despite otherwise good neurological recovery.
After stroke, extensive and severe impairment of information processing, dementia, occurs in 25% of elderly patients.
Also brain infarcts and white matter changes with ostensibly no clinical symptoms, are associated with an increased risk of a memory disorder.
In 15-20% of cases, progressive memory disorder is caused solely by a CVD, and in about 70% of these by small vessel disease. Mixed aetiologies are common especially in the eldest age groups, and in those, the impact of vascular factors on the progression of symptom picture is strong.
The classic risk factors (hypertension, high cholesterol concentration, diabetes, obesity, sedentary life style, smoking) of cardiovascular disease and CVD in middle-age are associated with an increased risk of memory disorder in more advanced age. Low educational level has also been found to increase the risk of memory disorders.
Extensive brain lesions caused by small vessel disease involve an increased risk of impaired information processing, dementia, depression, walking difficulty, falls, urinary tract symptoms, strokes, institutionalization, and death.
Symptoms and findings
Small vessel disease
An MRI scan of the brain will show diffuse white matter hyperintensities and/or lacunar infarcts in the deep grey and white matter. In addition, microhaemorrhages, expansion of perivascular spaces and cerebral atrophy may be found.
A typical cognitive early symptom is the slowing down of information processing and impairment of executive function. Executive function denotes control functions of information processing, such as planning, flexibility and assessment of one's own actions.
Memory impairment is often less pronounced than in Alzheimer's disease (AD). With increasing brain lesions the cognitive symptoms are, however, extensive.
Behavioural symptoms include depression, apathy and slower psychomotor speed.
Early clinical findings include:
minor signs of an upper motor neurone lesion (pronator drift, unilateral hyperreflexia, coordination problems)
micturition disturbances (urinary frequency and incontinence)
pseudobulbar symptoms, such as minor problems with articulation (dysarthria) and swallowing (dysphagia)
extrapyramidal symptoms (hypokinesia, rigidity).
Focal neurological deficits are very frequently subtle and limited to, for example, mild disturbances of balance and gait.
Symptom onset shows variation. The patient's past history often only reveals a transient ischaemic attack (TIA), momentary gait disturbances or confusion without clear focal neurological signs or symptoms suggestive of stroke.
Insidious disease onset is more common than sudden onset, and in the majority of patients the symptoms progress steadily without obvious stages of decline. However, symptoms may fluctuate showing day-to-day variation, and sometimes there are phases when no apparent change is noted in the condition even for several months.
Large vessel disease
Imaging studies typically show cortical and cortico-subcortical infarcts characteristic of large vessel disease or cardiac emboli. Haemorrhages are also possible.
Symptoms related to information processing vary depending on the site of lesion; symptoms related to executive function and memory, visual perception and speech can often be seen, as well as unilateral neglect, i.e. unilateral disturbance in directing attention.
Depending on the location of the infarcts, clinical findings may include hemiplegia and/or gait disturbances (hemiplegic and/or apractic-ataxic gait), visual field defects and/or drooping of the corner of the mouth.
Symptom onset is generally acute (hours, days), and the symptoms show stepwise progression (recovery after exacerbation) and fluctuation. If risk factors are well managed, patients can experience phases with no apparent deterioration in their condition often lasting up to a year.
Other findings
No typical findings can be obtained by currently available laboratory tests.
No markers specific for VCI alone can be detected in CSF.
Functional imaging studies (SPECT, PET) of the brain often show patchy hypoperfusion.
In case of AD + CVD, decreased beta-amyloid 42 in CSF can be seen, which is a biological marker of AD.
Treatment
The management of a memory disorder related to CVD concentrates on the causes and risk factors of CVD and on the treatment of other coexisting diseases, such as hypertension, hypercholesterolaemia and diabetes.
Preventive measures are very important, and patients should be encouraged to change their lifestyle early enough: no smoking, weight management, as well as sufficient exercise and sleep.
The benefit from physical exercise is based on its favourable effect on the management of CVD risk factors, and exercise also has a favourable effect on the brain-derived nerve growth factor.
Before old age, the risk of memory disorders can be reduced by treating hypertension. Too low blood pressure should be avoided in elderly people and those with extensive white matter changes.
Medication to prevent new circulatory disturbances should be prescribed according to stroke treatment guidelines. Clinical studies have not shown any differences in the effects of specific drugs (acetylsalicylic acid, dipyridamole, clopidogrel or anticoagulant therapy) in the symptomatic treatment of VCI.
VCI or vascular dementia is not an official indication for any pharmaceutical ingredient that has been studied in Europe (EMA) or in the United States (FDA).
Active lifestyle with versatile stimuli promote the maintaining of functional capacity.
Alzheimer's disease and CVD
AD and CVD share many risk factors: hypertension, hypercholesterolaemia, diabetes and arterial diseases.
Mixed AD + CVD is a significant subtype of progressive memory disease particularly in older age groups; at least half of patients over 80 with memory disorder have this subtype. Mixed memory disorder may turn out to be the most common single type of memory disorder.
Clinical diagnosis is difficult as the patients will have focal neurological symptoms and findings suggestive of CVD and simultaneously changes on cerebral imaging due to both CVD and AD.
Factors supporting the diagnosis of concurrent AD include a syndrome with predominantly early impairment of episodic memory, atrophy of the medial temporal lobe on MRI, as well as a decreased concentration of beta-amyloid 42 (Ab42) in CSF.
Patients with AD and coexisting CVD may benefit from AD memory medication.
Galanthamine is at least as effective here as in the treatment of AD alone. For donepezil, rivastigmine and memantine, there is no equivalent research evidence available.
References
Jokinen H, Koikkalainen J, Laakso HM et al. Global Burden of Small Vessel Disease-Related Brain Changes on MRI Predicts Cognitive and Functional Decline. Stroke 2020;51(1):170-178. [PubMed]
Kalaria RN. The pathology and pathophysiology of vascular dementia. Neuropharmacology 2018;134(Pt B):226-239. [PubMed]
Lo JW, Crawford JD, Desmond DW et al. Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups. Neurology 2019;93(24):e2257-e2271. [PubMed]