Introduction

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Background

Vascular dementia is the second most common form of dementia after Alzheimer disease (AD). The condition is not a single disease; it is a group of syndromes relating to different vascular mechanisms. Vascular dementia is preventable; therefore, early detection and an accurate diagnosis are important.

Patients who have had a stroke are at increased risk for vascular dementia. Recently, vascular lesions have been thought to play a role in AD.

As early as 1899, arteriosclerosis and senile dementia were described as different syndromes. In 1969, Mayer-Gross et al described this syndrome and reported that hypertension is the cause in approximately 50% of patients. In 1974, Hachinski et al coined the term multi-infarct dementia. In 1985, Loeb used the broader term vascular dementia. Recently, Bowler and Hachinski introduced a new term, vascular cognitive impairment.

Case study

A 70-year-old woman came to the clinic with her son for assessment of her cognitive decline. The son is concerned about her short-term memory problems for the past 10 months. Patient had a fall 10 months ago; after that fall, she started to ask the same questions over and over. Patient had another fall 4 months ago and also an episode of dizziness 2 months ago. With these incidents, her son noticed further decline in cognition. Recently, her son noticed that she has become a bit more suspicious of her daughter-in-law and has been hoarding things. She has lost interest in her day-to-day activities and forgets to include the right ingredients when cooking. Family has to remind her to take her medications, and her son is helping with the management of her finances.

The patient has hypertension, diabetes, coronary artery disease, osteoarthritis, and osteoporosis. On the Mini-Mental Status Examination (MMSE), the patient scored 21/30 with abnormal clock drawing. On the Geriatric Depression Scale (GDS), the patient scored 2/15. CT scan of the head showed multiple lacunar infarcts in the right basal ganglia and left cerebellar region.

Pathophysiology

Many subtypes of vascular dementia have been described to date. The spectrum includes (1) mild vascular cognitive impairment, (2) multi-infarct dementia, (3) vascular dementia due to a strategic single infarct, (4) vascular dementia due to lacunar lesions, (5) vascular dementia due to hemorrhagic lesions, (6) Binswanger disease, (7) subcortical vascular dementia, and (8) mixed dementia (combination of AD and vascular dementia).

Vascular dementia is sometimes further classified as cortical or subcortical dementia.

Vascular disease produces either focal or diffuse effects on the brain and causes cognitive decline. Focal cerebrovascular disease occurs secondary to thrombotic or embolic vascular occlusions. Common areas of the brain associated with cognitive decline are the white matter of the cerebral hemispheres and the deep gray nuclei, especially the striatum and the thalamus. Hypertension is the major cause of diffuse disease, and in many patients, both focal and diffuse disease are observed together. The 3 most common mechanisms of vascular dementia are multiple cortical infarcts, a strategic single infarct, and small vessel disease.

Mild vascular cognitive impairment can occur in elderly persons. It is associated with cognitive decline that is worse than expected for age and educational level, but the effects do not meet the criteria for dementia. These people have subjective and objective evidence of memory problems, but their daily functional living skills are within normal limits.

In multi-infarct dementia, the combined effects of different infarcts produce cognitive decline by affecting the neural nets.

In single-infarct dementia, different areas in the brain can be affected, which may result in significant impairment in cognition. This may be observed in cases of anterior cerebral artery infarct, parietal lobe infarcts, thalamic infarction, and singular gyrus infarction.

Small vessel disease affects all the small vessels of the brain and produces 2 major syndromes, Binswanger disease and lacunar state. Small vessel disease results in arterial wall changes, expansion of the Virchow-Robin spaces, and perivascular parenchymal rarefaction and gliosis.

Lacunar disease is due to small vessel occlusions and produces small cavitary lesions within the brain parenchyma secondary to occlusion of small penetrating arterial branches. These lacunae are found more typically in the internal capsule, deep gray nuclei, and white matter. Lacunar state is a condition in which numerous lacunae, which indicate widespread severe small vessel disease, are present.

Binswanger disease (also known as subcortical leukoencephalopathy) is due to diffuse white matter disease. In Binswanger disease, vascular changes observed are fibrohyalinosis of the small arteries and fibrinoid necrosis of the larger vessels inside the brain.

In cerebral amyloid angiopathy–associated vasculopathy, aneurysm formation and stenosis in the leptomeningeal and cortical vessels cause damage to the subcortical white matter. In hereditary cystatin-C amyloid angiopathy, patients have recurrent cerebral hemorrhages before age 40 years that can lead to dementia. Prevalence of cerebral amyloid angiopathy is consistently higher in patients with dementia than in patients without dementia, which indicates its significant role in the pathogenesis of dementia. ¹

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a rare autosomal dominant condition localized to chromosome arm 19q12 that affects small vessels supplying the deep white matter. Pathologically, multiple small infarcts are observed in the white matter, thalamus, basal ganglia, and pons.

Other less common syndromes may lead to vascular dementia. Rare arteriopathies such as inflammatory arteriopathy (eg, polyarteritis nodosa, temporal arteritis) and noninflammatory arteriopathy (eg, moyamoya disease, fibromuscular dysplasia) can cause multiple infarcts and can lead to vascular dementia. Hypoperfusion due to large vessel or cardiac disease can affect the watershed areas of the brain and lead to vascular dementia.

Leukoaraiosis greater than 25% is considered to be pathological. Subcortical vascular dementia is a diffuse small vessel disease with minimal or absent infarction with homogenous pathological and clinical features. ^{2 3} White matter ischemic changes affect executive dysfunction and cause slower processing speed, rather than memory and language impairment. ⁴

Arterial stiffness, which reflects an alteration in arterial mechanics, can be a risk factor for vascular dementia. ⁵

Mixed dementia is diagnosed when patients have evidence of Alzheimer dementia and cerebrovascular disease, either clinically or based on neuroimaging evidence of ischemic lesions. Growing evidence indicates that vascular dementia and Alzheimer dementia often coexist, especially in older patients with dementia. Autopsy studies have shown an association between Alzheimer disease and vascular lesions.⁶

Several recent studies also suggest that the risk of developing Alzheimer disease is increased when a patient is exposed to vascular risk factors such as hypertension, diabetes mellitus, peripheral arterial disease, and smoking, which usually are associated with cerebrovascular disease and vascular dementia. Recent evidence suggests that the vascular processes in both disorders may mutually induce each other. Apolipoprotein E may play a role in Alzheimer disease and vascular dementia. Apolipoprotein E4 also increases the risk of dementia in stroke survivors and is a strong risk factor for the development of cerebral amyloid angiopathy in patients with Alzheimer disease. In elderly individuals, many cases of dementia may be caused by the cumulative effect of cerebrovascular and Alzheimer pathology.

One-third of patients with vascular dementia are found to have significant Alzheimer disease pathology with cholinergic deficits in the nucleus basalis of Meynert. ⁷

Vascular cognitive disorder (VCD) is a new term used to describe a particular constellation of cognitive and functional impairment spectrum that ranges from vascular cognitive impairment (VCI) to subcortical vascular dementia, poststroke dementia, and mixed dementia. ³

Frequency

International

• Vascular dementia is the second most common cause of dementia in the United States and Europe, but it is the most common form in some parts of Asia.
• The prevalence rate of vascular dementia is 1.5% in Western countries and approximately 2.2% in Japan.
• In Japan, vascular dementia accounts for 50% of all dementias that occur in individuals older than 65 years.
• In Europe, vascular dementia and mixed dementia account for approximately 20% and 40% of cases, respectively.
• In Latin America, 15% of all dementias are vascular.
• In community-based studies in Australia, the prevalence rate for vascular and mixed dementia is 13% and 28%, respectively.
• The prevalence rate of dementia is 9 times higher in patients who have had a stroke than in controls. One year after a stroke, 25% of patients develop new-onset dementia. Within 4 years following a stroke, the relative risk of incident dementia is 5.5%.

Mortality/Morbidity

• In patients with dementia who have had a stroke, the increase in mortality is significant. The 5-year survival rate is 39% for patients with vascular dementia compared with 75% for age-matched controls. ⁸
• Vascular dementia is associated with a higher mortality rate than AD, presumably because of the coexistence of other atherosclerotic diseases.
• Study on causes of death in patients with dementia showed that circulatory system disorders (eg, ischemic heart disease) is the most common immediate cause of death in vascular dementia, followed by respiratory system diseases (eg, pneumonia). ⁹

Sex

• The prevalence of vascular dementia is higher in men than in women.

Age

• Incidence increases with age.

Clinical

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History

Cognitive impairment, acutely or subacutely, after an acute neurologic event with a stepwise progression is a typical history suggestive of vascular dementia. However, this classic history is usually observed with multi-infarct dementia and may not be observed with lacunar state.

• Binswanger disease
  • The average age of onset is between the fourth and seventh decades of life, and 80% of patients have a history of hypertension.
  • Patients also show progressive motor, cognitive, mood, and behavioral changes over a period of 5-10 years. Mood and behavioral changes are observed early and, in some patients, may be the presenting feature.
  • Patients may be apathetic or abulic.
  • Intellectual deficits are also observed early in the disease, and patients are frequently described as disoriented, having memory deficits, inattentive, and vague.
  • Patients with Binswanger dementia often have early-onset urinary incontinence and gait disturbances.
• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
  • The onset of the disease occurs between the third and fourth decades of life.
  • The clinical picture is similar to Binswanger disease but without a history of hypertension and risk factors for cerebrovascular disease.
• Vascular dementia in general
  • Health professionals can perform a Mini-Mental Status Exam (MMSE), ¹⁰ depression assessment screen using DSM-IV-TR criteria, ¹¹  the Geriatric Depression Scale (GDS), ¹² or the Cornell Scale for depression in dementia, ¹³ They should also assess for suicidal and homicidal risk, if necessary. Health professionals can directly ask patients about suicidal or homicidal ideation (thoughts), intent, and plan.
  • Major depression is widely observed mood disorder in vascular dementia. Elderly demented patients may not endorse depressed mood and may be socially withdrawn with decreased psychomotor activity. Suicidal thoughts, intent, passive wishes to die and feeling that life is not worthy is seen in these patients and they should be followed closely. Suicide attempts were observed in fewer than 1% of patients with dementia, and depression is an important reason for that. ¹⁴
  • Demented patients will develop psychosis, delusions, hallucinations and paranoia at some point in their disease and sometimes agitation can be dangerous when it manifests into abnormal behavior and in rare circumstances can lead to attempts of homicide.
  • The mental status is a bedside or interview assessment and includes the patient's appearance, affect (mood), thoughts (especially the presence of hallucinations and delusions), inquiry into self-destructive behavior, homicidal behavior, judgment, and, in this diagnosis, orientation, immediate, recent, and long-term memory.
  • Patients with vascular dementia commonly have mood and behavioral changes.
  • Severe depression is more common in persons with vascular dementia than in those with AD.
  • In some patients with lacunar state and Binswanger disease, such problems may be more prominent than intellectual deficits.
  • Even psychotic symptoms, particularly delusions, have been described in patients with vascular dementia.
  • Emotional lability may be a prominent symptom in some patients.
  • Executive functioning deficits are seen prior to severe memory loss in the early stages of subcortical vascular cognitive impairment. ¹⁵

Physical

A commonly used cognitive screening tool is the Folstein Mini-Mental State Examination. Patchy defects are present in persons with vascular dementia. The deficits are global in persons with Alzheimer dementia.

• The Folstein Mini-Mental State Examination is as follows:
  • Orientation: First, ask the patient the date, day, month, year, and season. The maximum score is 5. Second, ask the patient their current location, ie, facility, floor, town, state, and country. The maximum score is 5.
  • Registration: Name 3 objects (eg, ball, flag, door), and ask the patient to repeat them. The maximum score is 3.
  • Attention: Ask the patient to spell the word "world" backwards or to subtract 7 from 100 serially backwards (stop after 5 answers). The maximum score is 5.
  • Recall: Ask the patient to remember the 3 objects from the Registration portion of the test. The maximum score is 3.
  • Language
    • Ask the patient to identify a pencil and a watch. The maximum score is 2.
    • Ask the patient to repeat the phrase "no ifs, ands, or buts." The maximum score is 1.
    • Ask the patient to follow a 3-step command. The maximum score is 3.
    • Ask the patient to read and obey the phrase "close your eyes." The maximum score is 1.
    • Ask the patient to write a sentence. The maximum score is 1.
    • Ask the patient to copy a set of interlocking pentagons. The maximum score is 1.
  • Scoring: The maximum score possible is 30. Generally, any score less than 24 is considered abnormal, but the cutoff varies with the patient's level of education. Because the results for this test can vary over time, and for some people results can vary during the day, record when (ie, the time and date) this test was performed.
    
• Several specific diagnostic criteria can be used to diagnose vascular dementia, including the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria, the International Classification of Diseases, Tenth Edition criteria, the National Institute of Neurological Disorders and Stroke-Association International pour la Recherché at L'Enseignement en Neurosciences (NINDS-AIREN) criteria, the Alzheimer's Disease Diagnostic and Treatment Center criteria, and the Hachinski ischemic score.
  
• The DSM-IV-TR criteria have good sensitivity but low specificity. A summary of the DSM-IV-TR diagnostic criteria is as follows:
  • The patient has developed multiple cognitive deficits manifesting as both (1) memory impairment and (2) one or more of the following cognitive disturbances: aphasia, apraxia, agnosia, and disturbance in executive functioning.
  • The cognitive deficits in the above criteria cause significant impairment in day-to-day functioning, social or occupational functioning and represent a significant decline from the previous level of functioning.
  • Focal neurologic signs and symptoms or radiologic evidence indicative of cerebrovascular disease are present that are judged to be etiologically related to the dementia.
    
  • The deficits do not occur exclusively during the course of delirium.
• The NINDS-AIREN criteria are the most specific of all available criteria and are used most commonly in research. They provide 3 levels of certainty: definite, probable, and possible.
  
• Lateralizing signs such as hemiparesis, bradykinesia, hyperreflexia, extensor plantar reflexes, ataxia, pseudobulbar palsy, and gait and swallowing difficulties may be observed.
  
• Subcortical vascular dementia signs include balance problems, gait disorder, and urinary incontinence; focal lesions may be subtle.
  
• Neuropsychological testing is as follows:
  • Patients with vascular dementia have patchy neuropsychological deficits. With vascular dementia, patients have better free recall and fewer recall intrusions compared with patients with AD. Apathy early in the disease is more suggestive of vascular dementia because it usually occurs in the later stages of AD.
  • Patients with vascular dementia have poor verbal fluency and more perseverative behavior compared with patients with AD. They may even have other signs of executive dysfunction such as cognitive slowing, difficulty in shifting sets, and problems with abstraction. Commonly used mental status tests include the Folstein Mini-Mental State Examination and the Cognitive Abilities Screening Instrument.
  • Some cognitive patterns may help to differentiate vascular dementia clinically from AD. Patients with vascular dementia tend to show greater deficits on measures of frontal executive functioning than patients with AD, whereas patients with AD show greater long-term memory deficits than patients with vascular dementia.
  • Neuropsychological findings vary with the site and severity of cerebrovascular disease.
  • For patients with single or multiple large infarcts, deficits correlate with the site and extent of the infarct.
  • In patients with extensive deep white matter disease, impairments may be observed in tests of psychomotor speed, dexterity, executive function, and motor aspects of speech (eg, dysarthria, reduced verbal output). Patients with subcortical vascular dementia show reduced ability to set and reach goals with mental slowing and gradual executive dysfunction.
    
• Behavioral problems assessment: Behavioral disturbances are common in dementia and are associated with adverse outcomes, increased disability, caregiver stress, and earlier institutionalization. Patients should be assessed for the following disturbances:
  • Agitation/aggression: Patient exhibits restlessness, physical agitation, or verbal or sexual aggression. Patient is hard to handle or resistant to care.
  • Hallucinations: Patient sees or hears things that are not there.
  • Delusions/paranoia: Patient harbors false beliefs, is suspicious of family members regarding stealing money or belongings, or suspects neighbors are planning to harm him.
  • Sundowning: Abnormal behaviors typically occur in the late afternoon or evening in a circadian rhythm fashion. Patients may exhibit mood swings, become upset or disoriented, or wander.

Causes

• Risk factors for vascular dementia include hypertension, smoking, hypercholesterolemia, diabetes mellitus, and cardiovascular and cerebrovascular disease.

DIFFERENTIAL DIAGNOSIS

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Dementia Due to Head Trauma
Dementia Due to HIV Disease
Depression
Huntington Disease Dementia
Parkinson Disease Dementia

Other Problems to Be Considered

Alzheimer disease
Brain tumor
Creutzfeldt-Jakob disease
Neurosyphilis
Normal pressure hydrocephalus
Frontotemporal dementia
Pick disease
Lewy body dementia

Patients with AD have early language and visuospatial deficits. The deficits in short-term memory are severe, and clues do not help in retrieving information. The onset of the disease is gradual, with a slow progression. Usually, no motor findings are present until the middle or late stages of the disease.

Patients with vascular dementia have patchy cognitive impairment, often with focal neurologic signs and symptoms. Onset may be abrupt, with a stepwise decline.

Patients with Parkinson dementia have cognitive slowing with extrapyramidal signs such as rigidity, bradykinesia, tremor, and gait disturbances. Usually, dementia is seen in later stages of the disease.

Patients with dementia due to head trauma have memory impairment, and other cognitive deficits associated with a history of head trauma occur. The physical findings depend on the location of injury. Usually, it is not progressive unless the person has a history of repeated head trauma (eg, dementia pugilistica).

Patients with HIV dementia have a positive result from an HIV test and cognitive changes with neurological signs.

Frontotemporal dementia is a type of cortical dementia characterized by behavioral and personality disorders more than cognitive issues. Three distinct types are seen: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia.

Patients with Pick disease have memory problems, personality changes, and deterioration of social skills. Onset is usually between the fifth and sixth decades of life. Upon physical examination, the patient has frontal release signs such as snout and grasp reflex.

Huntington disease is an autosomal dominant disease with an onset of cognitive changes as early as the third decade of life, with physical signs of choreoathetosis.

In Creutzfeldt-Jakob disease, onset is usually seen between the fourth and sixth decades of life, even though it can occur at any, and is associated with signs such as myoclonus, seizures, and ataxia. A rapid progression is typical.

Patients with Lewy body dementia have recurrent visual hallucinations, fluctuating cognitive impairment, and parkinsonism features. Also, the frequency of adverse reactions to antipsychotic medications is high.

In the case of cognitive symptoms secondary to depression, the onset is acute compared with the insidious onset in most types of dementia. The term pseudodementia has been used to describe the condition when cognitive symptoms are prominent. The current and more accurate name for this state is dementia of depression. Patients with depression usually report their cognitive difficulties, which is unusual for patients with dementia. Patients with depression tend to state that they do not know the answers to questions, and they appear to not try very hard during neuropsychological evaluations. Mood symptoms are prominent in patients with dementia of depression.

WORKUP

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LABORATORY STUDIES

• Laboratory tests should be performed to rule out other causes of dementia. These tests should routinely include a CBC count, erythrocyte sedimentation rate, glucose level, renal and liver function tests, serologic tests for syphilis, vitamin B-12 and red blood cell folate levels, and thyroid function tests
  .
• In selected patients, optional tests include HIV serology testing, lupus anticoagulant testing, antiphospholipid antibody testing, antinuclear antibody testing, and antineutrophil cytoplasmic antibody testing.

• Neuroimaging studies may include CT brain scanning and MRI of the brain.
  • The absence of cerebrovascular lesions on CT scanning or MRI is evidence against vascular etiology.
  • The features on CT scanning or MRI that are suggestive of vascular dementia are bilateral multiple infarcts located in the dominant hemisphere and limbic structures, multiple lacunar strokes, or periventricular white matter lesions extending into the deep white matter.
  • Patients with vascular mild cognitive impairment (MCI), which is a prodromal stage for subcortical vascular dementia, have MRI features that differ from patients with amnestic MCI, which is the prodromal stage for AD. Vascular MCI shows more extensive white matter lacunar infarcts and leukoaraiosis and minimal hippocampal and entorhinal cortical atrophies, whereas the opposite is true for amnestic MCI.
    
• Functional imaging studies include the following:
  • According to a 2000 study by Nagata et al,16 positron emission tomography may be useful for differentiating vascular dementia from AD. Hypoperfusion and hypometabolism can be observed in the frontal lobe, including the cingulate and superior frontal gyri, in patients with vascular dementia; a parietotemporal pattern is observed in patients with AD.
  • Starkstein et al in 199617 and other authors have demonstrated that single-photon emission CT scanning produce similar findings.
    
• Cerebral angiography is not performed routinely during the evaluation of vascular dementia, but it is performed before carotid artery surgery. It also is useful in cases of possible cerebral vasculitis; cerebral vessels can demonstrate beading.

• Tests that may be useful for evaluation of stroke and in certain cases of vascular dementia include the following:
  o Echocardiography
  o Holter monitoring
  o Carotid duplex Doppler scanning

TREATMENT

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MEDICAL CARE

The mainstay of management of vascular dementia is the prevention of new strokes. This includes administering antiplatelet drugs and controlling major vascular risk factors. Aspirin has also been found to slow the progression of vascular dementia.

• Recent guidelines from the American Psychiatric Association provide both treatment principles and possible specific therapies.
  • Drug treatment is primarily used to prevent further worsening of vascular dementia by treating the underlying disease such as hypertension, hyperlipidemia, and diabetes mellitus. Antiplatelet agents are indicated.
  • Pentoxifylline and, to a more limited extent, ergoloid mesylates (Hydergine), may be useful for increasing cerebral blood flow. In the European Pentoxifylline Multi-Infarct Dementia Study, which is a double-blinded, placebo-controlled, multicenter study, treatment with pentoxifylline was found to be beneficial for patients with multi-infarct dementia. Significant improvement was observed in the scales used for assessing intellectual and cognitive function.
  • Neuroprotective drugs such as nimodipine, propentofylline, and posatirelin are currently under study and may be useful for vascular dementia. Nicardipine is a dihydropyridine calcium channel blocker that was studied on the treatment of cognitive deterioration of vascular origin. Preliminary studies showed decrease in cognitive deterioration in patients with cerebrovascular disease.18
  • Increasing evidence supports the involvement of the cholinergic system in vascular dementia, similar to that seen in Alzheimer dementia. However, no cholinesterase inhibitors have been approved to date for the treatment of vascular dementia, despite positive results in clinical trials with this medication.
    
• The general management of dementia includes appropriate referral to community services, judgment and decision-making regarding legal and ethical issues (eg, driving, competency, advance directives), and consideration of caregiver stress.

DIET

• In the Rotterdam study, an increased risk of vascular dementia was associated with total fat intake, whereas fish consumption was inversely related to dementia.
  
• Low levels of folate, vitamin B-6, and vitamin B-12 are associated with increased homocysteine levels, a risk factor for stroke.

MEDICATION

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Medical therapy options include antiplatelet and hemorheologic agents.

ANTIPLATELET AGENTS

Studies have shown antiplatelet agents are useful for preventing recurrent stroke. In vascular dementia, a pilot study showed that aspirin has positive effects on cognitive deficits. Recent studies have shown it may have some neuroprotective effects. Other antiplatelet agents are ticlopidine and clopidogrel.

Prevents platelet-aggregating thromboxane A2 by blocking prostaglandin synthetase action and thereby preventing prostaglandin synthesis.

Aspirin (Anacin, Ascriptin, Bayer aspirin)

Prevents platelet-aggregating thromboxane A2 by blocking prostaglandin synthetase action and thereby preventing prostaglandin synthesis.

Dosing
Adult

325 mg PO qd

Pediatric
Not established

Interactions

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses > 2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs

Contraindications

Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; use in children ( <16 y) with flu (associated with Reye syndrome)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants

Used in patients who cannot tolerate aspirin therapy or in whom aspirin therapy fails.

Dosing
Adult

250 mg PO bid

Pediatric

Not established

Interactions

Effects may decrease with coadministration of corticosteroids and antacids; toxicity increases when taken concurrently with theophylline, cimetidine, aspirin, and NSAIDs
Contraindications

Documented hypersensitivity; neutropenia or thrombocytopenia; liver damage; active bleeding disorders
Precautions
Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Discontinue if absolute neutrophil count decreases to <1200/µL or if platelet count falls to <80,000/µL

Antiplatelet drug that acts by direct inhibition of ADP binding to the platelet receptor and of subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex.
Dosing
Adult

75 mg PO qd

Pediatric

Not established

Interactions

Coadministration with naproxen associated with increased occult GI blood loss; prolongs bleeding time; safety of coadministration with warfarin not established

Contraindications

Documented hypersensitivity; active pathological bleeding (eg, peptic ulcer); intracranial hemorrhage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions

Use caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (eg, ulcers)

In a multicenter, double-blinded, placebo-controlled trial involving 29 European centers, improvement in cognitive function at 9 mo was noted.

Dosing
Adult

400 mg PO tid

Pediatric

Not established

Interactions

Coadministration with cimetidine or theophylline increases effects and toxic potential; increases effect of antihypertensives

Contraindications

Documented hypersensitivity; cerebral or retinal hemorrhage

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment

FOLLOW-UP

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• If depressed patients do not respond to medical management or if the depression is severe (ie, with life-threatening behavior such as suicide attempts), electroconvulsive therapy is indicated and patients should be hospitalized.
  
• As dementia progresses, more troubling behaviors such as agitation, aggression, wandering, sleep disorders, and inappropriate sexual behavior are observed. The decision for placement in institutions is usually made when problem behaviors become unmanageable, when more assistance is necessary in performing activities of daily living, when caring duties exceed the capacity of the caregiver, or when a breakdown in the family caregiver's health occurs.

Further Outpatient Care

• Regular follow-up every 4-6 months is recommended to assess the patient's general condition and cognitive and noncognitive symptoms.
  
• Frequent visits may be needed for patients with behavioral problems and patients who are on specific therapies such as neuroprotective agents.
  
• Treatment of risk factors such as hypertension, hypercholesterolemia, and diabetes mellitus require special attention.

Deterrence/Prevention

• Vascular cognitive impairment is modifiable and preventable.
  • Modifying vascular risk factors (eg, hypertension, diabetes mellitus, smoking, hyperhomocystinemia) and dietary factors (eg, hypercholesterolemia) in midlife may help to prevent stroke and vascular dementia. The single most important risk factor is hypertension. Epidemiologic cohort studies and intervention trials with antihypertensive medications demonstrated the usefulness of antihypertensive drugs in the prevention of vascular dementia.
    
  • Appropriate treatment for atrial fibrillation, coronary artery disease, congestive heart failure, and stroke is also recommended.
    
  • Adequate management of vascular risk factors, stroke, and heart disease in middle age may be the most effective way to prevent vascular dementia later in life. The distinction between vascular dementia and Alzheimer dementia is becoming increasingly blurred because vascular risk factors play a role in both diseases.
    
• In patients with early cognitive impairment or with neuroimaging findings that demonstrate leukoaraiosis or stroke, secondary prevention can be facilitated by applying standard stroke-preventive therapies such as antiplatelet agents, warfarin, or carotid endarterectomy according to accepted guidelines.

Complications

• Behavioral problems, including wandering, delusions, hallucinations, and poor judgment
• Depression
• Falls and gait abnormality
• Aspiration pneumonia
• Decubitus ulcers
• Caregiver burden and stress: This should be considered a complication of any dementia, including vascular dementia. This can lead to increased psychiatric and medical morbidity in the caregiver.

Prognosis

• According to some studies, vascular dementia shortens life expectancy by approximately 50% in men, in persons with lower education, and in persons who perform worse on neuropsychological tests.
• The causes of death are due to complications of dementia, cardiovascular disease, and miscellaneous factors, including malignancy.

PATIENT EDUCATION

Patient and family education

• Caregiver education is important to dementia management.
  • Structured, respectful, and friendly caregiving is best, and it forms the most important aspect of behavioral care for patients with vascular dementia.
  • Educating the caregiver on how to take care of these patients, how to react to certain behaviors and agitation, and how to reorient the patient improves the quality of care and treatment in these patients.
  • Well-informed caregivers are best equipped to address the problems that vascular dementia presents.
    
• Guidelines for caregiver education are as follows:
  • Use short simple sentences when communicating with patients with dementia.
    
  • Simplify and create a routine for all self-care tasks such as bathing and dressing.
    
  • Establish a daily routine for all activities such as meals, medication administration, recreation, exercise, and sleep.
    
  • To reorient the patient, use signs and pictures, clocks and calendars, family photos, and a list of daily activities.
    
  • Use distraction, not confrontation, to control irritable or socially inappropriate behaviors.
    
• Initiate discussion about long-term care planning, including nursing home placement and issues regarding caregiver stress and respite care. Respite care is a community resource that gives the caregiver relief for a short period.
• Day programs can also provide relief for families, particularly working families, and can provide structure and activities for patients with dementia.
• Additional patient and family education can be accessed at the following sites:
  
  • Alzheimer's Association: Vascular Dementia
  • National Institute of Neurological Disorders and Stroke: NINDS Multi-Infarct Dementia Information Page
    
• For excellent patient education resources, visit eMedicine's Dementia Center and Stroke Center. Also, see eMedicine's patient education articles Dementia in Head Injury, Dementia Overview, Possible Early Dementia, Dementia Medication Overview, Stroke, and Stroke-Related Dementia.
  
• See other resources for caregivers at The National Institute on Aging and Family Caregiver Alliance.
  

MISCELLANEOUS

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Medicolegal Pitfalls

• Dementia is a condition of impaired memory and cognition. Early in the course of vascular dementia, competence and capacity may be relatively intact. Patients may be able to manage their own affairs, provide consent for medical treatments, execute living wills, or nominate a durable power of attorney for health care and finances.
  
• As the dementia progresses, competency and capacity are impaired. Sometimes, severe incapacitating dementia can occur before protective legal decisions are made. In such instances, the court may need to appoint a guardian, conservator, or trustee. The term trustee applies to a person appointed by law to execute a trust for the benefit of the beneficiary. A guardian or conservator is a person who has the legal power to take care of and/or manage the property of an incompetent person.

Special Concerns

• Ethical issues must be considered on an individual basis, with consideration of clinical judgment and general ethical principles.
  
• Frequently arising ethical issues and dilemmas in the care of individuals with vascular dementia are as follows:
  • Dementia and driving
  • Consent for treatment and care
  • Physical and chemical restraints
  • Issues of end-of-life care, including artificial nutrition and hydration