Vascular dementia: a brief overview for the practitioner

The population of the European Union is aging, therefore the number of people suffering from dementia is increasing. This forces scientists, practicing doctors, various state institutions to pay more attention to dementia prevention, more effective treatment, and improvement of medical and social services.

Prevalence of Dementia in Europe

Dementia is one of the most severe and common diseases among older people. Currently, about 2.5 million men and 3 million women living in the European Union are affected by it. Data shows that there are slightly more cases of dementia in Northwestern Europe than in Southern Europe. It is estimated that about half a million new cases of dementia will be diagnosed annually in the European Union.

The most common forms of dementia are Alzheimer's disease (AD) (60–70% of cases), vascular dementia (VD) (15% of cases), and dementia with Lewy bodies (DLB) (15% of cases). According to the pathogenesis mechanism, dementia is either of neurodegenerative origin (AD and DLB) or a consequence of impaired brain circulation (VD).

Signs of Dementia

The most important signs of dementia can be divided into several groups:
• cognitive impairment;
• decreased functional independence;
• neuropsychiatric symptoms.
Dementia usually starts and progresses slowly. Although many older people complain of memory problems (e.g., difficulty remembering names, slower recall of necessary information), it does not interfere with their daily lives. Moreover, considering cognitive decline as an inevitable companion of old age and ignoring it is a misconception still prevalent in our society. When memory impairment is more severe than expected for age and other dementia criteria are not met, it is called mild cognitive impairment (MCI). MCI does not necessarily indicate the onset of dementia as it may be related to depression or other conditions. However, individuals with MCI are more likely to develop AD several times, so it is recommended to evaluate patients experiencing MCI symptoms. This can lead to an earlier diagnosis and treatment of AD or adjustment of vascular risk factors and implementation of stroke prevention measures.
It is important not to forget that there are conditions that can manifest as dementia symptoms. The condition of such a patient deteriorates continuously, and as cognitive functions decline, progressive dementia may be suspected. Therefore, these treatable conditions must be ruled out. It is crucial to accurately diagnose the disorder because the patient's recovery/improvement depends on the appropriate treatment, which varies depending on the form of dementia. The causes of some treatable conditions are listed in Table 1.

1 Table. Possible causes of conditions similar to dementia

Vascular Dementia

Vascular dementia is a cognitive impairment caused by cerebrovascular diseases that disrupt daily activities and meet the criteria for vascular dementia according to NINDS-AIREN (National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherché et l'Enseignement en Neurosciences).
Risk factors for vascular dementia include age, arterial hypertension, low education level, ischemic heart disease, atrial fibrillation, diabetes mellitus, smoking, hypercholesterolemia, obesity. It has been observed that an important risk factor for dementia (both vascular and AD) is depression.
Before dementia manifests, a patient may have experienced one or several ischemic strokes due to blockage of blood vessels in the brain, less frequently - due to bleeding into the brain. However, most often dementia is caused by multiple small cerebral infarctions due to atherosclerosis or lipohyalinosis. Occasionally, vascular dementia can develop without experiencing a stroke, due to diffuse or multi-infarct damage to the white matter of the brain (Table 2).

Table 2. ICD-10 codes for vascular dementia

Early signs of vascular dementia include urinary and gait disturbances. Patients often experience various somatic complaints (headaches, dizziness, impaired balance, etc.), emotional disturbances (lability, tearfulness, anger, irritability), personality changes (lack of self-criticism, aggressiveness, irritability, sexual dysfunction), loss of orientation in time and space, especially in the evenings or at night.
A previous stroke often causes varying degrees of cognitive impairment. However, memory impairments are not usually prominent at the onset of vascular dementia; they worsen in later stages of the disease. The most dangerous period for the development of vascular cognitive impairment is the first 3 months after a stroke.
Some form of cognitive dysfunction is detected in 50-75% of cases after a stroke; vascular dementia develops in about 25% of patients within 3 months, and a previous stroke increases the risk of dementia by about 9 times and can worsen the course of existing dementia.
Cognitive impairments often progress in stages, along with accompanying motor disturbances. The patient's disability is greatly increased by attention, memory, and executive function impairments. Parkinsonism-like symptoms (amimia, rigidity), asymmetry of tendon reflexes, pathological plantar reflexes, and other focal neurological symptoms, oral automatisms, and heightened jaw jerk reflex are often present.

Importance of Imaging Studies
It is increasingly recognized that the most important method for diagnosing cognitive impairments is imaging studies. Recently, practical recommendations have been proposed that computerized tomography (CT) or magnetic resonance imaging (MRI) be performed at least once for patients with dementia. If possible, MRI is preferred - it provides a clearer and more contrasting image than CT, making vascular changes and atrophy more visible.
Traditionally, CT and MRI for patients with cognitive impairments were performed to rule out causes requiring surgical treatment: tumors, hematomas, hydrocephalus. Although this is important, these studies are now more often performed for their positive prognostic value than just to determine other causes. Imaging studies can demonstrate cerebrovascular diseases and partially differentiate vascular dementia from Alzheimer's disease.
Widespread hyperintensity and signal changes in the basal ganglia and brainstem suggest insufficient cognitive function. Unfortunately, pathology is often intertwined, making it difficult to differentiate between Alzheimer's disease, vascular dementia, and other conditions.

Treatment of Vascular Dementia
When treating cerebrovascular dementia, it is important to control the risk factors for cerebrovascular diseases of the brain. New data on CVD and AL as concomitant diseases encourage improving dementia prevention measures by actively controlling their risk factors: arterial hypertension, elevated cholesterol and homocysteine concentrations, atrial fibrillation, obesity, and smoking. Also important are treatment measures usually applied for primary and secondary prevention of cerebrovascular disease and myocardial infarction. Therefore, antithrombotic, antilipidemic, antihypertensive drugs are prescribed, as well as drugs that improve brain blood flow and metabolism: nootropic drugs (piracetam, pramiracetam (Pramistar)), vinpocetine, standardized Ginkgo biloba extract (EGb 761). In addition to the listed drugs, nicergoline was previously used for treatment. However, in 2013, the European Medicines Agency urged to ban nicergoline group preparations in the European Union member states because they increase the risk of fibrosis and ergotism, outweighing the potential benefit. Therefore, nicergoline is no longer used in Lithuania.
Treatment with cognition-enhancing drugs should be initiated after the acute stroke period.
Nootropic drugs are a heterogeneous group of preparations that improve cognitive functions in dementia and other diseases. These drugs activate the cholinergic system, thus increasing acetylcholine concentration; activate brain metabolism; increase the ATP/ADP ratio and cAMP levels; promote phospholipid metabolism and protein synthesis; increase glucose and oxygen utilization when brain metabolism decreases; enhance local perfusion; modulate ion metabolism; act as antioxidants. Nootropic drugs differ from other cognition-enhancing drugs in that they actively affect the corpus callosum area.
Pramiracetam (Pramistar) is a piracetam derivative characterized by 8-30 times stronger effects than its precursor. It acts in three ways: reducing neuropeptidase activity, enhancing the effect of methamphetamine, activating acetylcholine metabolism. As a result, not only short-term but also long-term memory, attention, and to some extent, depression are improved. Studies have shown that pramiracetam enhances memory and information absorption. The drug has no inhibitory effect and does not affect the autonomic nervous system. Studies have shown that in cases of acute ischemic stroke, pramiracetam improves microcirculation, neurotransmitter functions, and neuron metabolism. Based on research data, the use of pramiracetam and other nootropic drugs facilitates adaptation, accelerates the recovery of impaired neurological functions. In cases of chronic cerebral circulation insufficiency, when memory significantly deteriorates due to a lack of mediators, treatment with pramiracetam is more effective than placebo. In a placebo-controlled trial, the efficacy of pramiracetam in treating men with impaired cognitive functions due to brain trauma and anoxia was evaluated. According to the study data, the effect of pramiracetam exceeded that of placebo.
Pramistar is prescribed for the treatment of age-related degenerative or cerebrovascular memory and attention disorders. The results of clinical trials show that pramiracetam is well tolerated by older people. The drug is usually taken at a dose of 600 mg twice a day, with the effect becoming apparent after 4-8 weeks of treatment, although the dose and onset of action may vary individually for each patient. Since nicergoline is no longer used in Lithuania, the role of pramiracetam in treating cerebrovascular circulation disorders that impair cognitive functions becomes very significant.
Standardized Ginkgo biloba extract (EGb 761) accelerates the ability of neurotransmitters to bind to membrane receptors, acts on the vascular system and cell metabolism, and improves blood rheological properties.
In 2007, a systematic review was published to evaluate the results of randomized clinical trials of donepezil, rivastigmine, galantamine (for the treatment of cerebrovascular dementia). The conclusion was that the currently available data do not support the use of these drugs in treating cerebrovascular dementia in routine clinical practice.
Some scientists point to the positive effect of cerebrolysin - a low molecular weight peptide and free amino acid solution, a preparation of pig brain peptides - on cognitive functions in cases of cerebral circulation insufficiency.Two newest methods have been introduced for the treatment of dementia: light therapy and aromatherapy. Randomized controlled trials have confirmed that both of these methods are effective in improving the behavior of individuals with dementia.

Conclusions
• Dementia usually starts and progresses slowly, disrupting cognitive functions, the patient's functional independence, and manifesting in various neuropsychiatric symptoms.
• When treating vascular dementia, it is recommended to use drugs that improve cerebral blood flow and metabolism, and have a favorable effect on cognitive functions: nootropics (piracetam, pramiracetam (Pramistar)), vinpocetine, standardized Ginkgo biloba extract (EGb 761).
• Treatment with drugs that affect cognitive functions should start after the acute phase of a stroke, using the recommended doses by the manufacturer for at least several months.
• Pramiracetam (Pramistar) is a well-tolerated and effective drug that enhances short-term and long-term memory, attention concentration, and has an antidepressant effect.
• The best way to treat psychiatric and behavioral disorders in dementia patients is a combination of nursing care, psychosocial measures, and medication.


Prepared by Dr. A. Pilkauskas
LT/Pra/2014/01


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