Vascular Dementia and Vascular Cognitive Impairment

A 74-year-old man presented to the clinic with a six-year history of cognitive and functional decline. His family reported that his problems began with “small TIAs.” When we asked them what they meant, they explained that he appeared to be suffering from transient ischemic attacks, such that in a single day he might show a sudden decline in his speech, handwriting, and gait, which would subsequently improve, although not back to his baseline. Despite earning a degree in engineering, he had difficulty at that time with simple calculations, such as calculating the tip in a restaurant. He also had difficulty remembering a short list of items, and finding his way around a familiar street. His family also reported that he would often cry or laugh either inappropriately or with the least provocation.

Quick Start

Definition	• Vascular cognitive impairment occurs when cognitive dysfunction is due to cerebrovascular disease (i.e., strokes). • Vascular dementia occurs when cerebrovascular disease causes both cognitive dysfunction and impairment in daily functioning. • The exact cerebrovascular disease that can cause cognitive and functional impairment may be varied, and can include: • Small vessel ischemic disease • Multiple cortical strokes • Strategic infarcts • Cerebral amyloid angiopathy.
Prevalence	• Approximately 5–10% of patients with dementia have a pure vascular dementia, that is, dementia entirely attributable to cerebrovascular disease. • Another 10–15% of patients with dementia suffer from a mixed dementia of cerebrovascular disease plus a neurodegenerative disease.
Genetic risk	• The genetic risk is related to the varied underlying cerebrovascular pathology. • One disorder, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), is due to mutation of the Notch3 gene at the chromosome locus 19p13.
Cognitive symptoms	• Neuropsychological testing typically shows impairment in multiple domains, including attention, frontal/executive function, and speed of processing. Memory impairments are typically secondary to attention and frontal/executive dysfunction.
Diagnostic criteria	• The history shows the signs and symptoms of strokes and often reveals a stepwise decline. • The neurological examination shows evidence of strokes including focal signs and extensor plantar reflexes. • Neuropsychological testing typically shows impairment in multiple domains, including attention, frontal/executive function, and speed of processing. Memory impairments are typically secondary to attention and frontal/executive dysfunction. • To make a diagnosis of vascular dementia or vascular cognitive impairment, the CT or MRI scan shows sufficient cerebrovascular disease to explain the cognitive dysfunction. • Formal diagnostic criteria are available from the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) and the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).
Behavioral symptoms	• Depression is often present.
Treatment	• There are no FDA-approved medications to treat vascular dementia and vascular cognitive impairment. However, clinical trials have found both cholinesterase inhibitors and memantine to be helpful. For memory problems we recommend a trial of cholinesterase inhibitors, and for apathy we recommend a trial of memantine. • Dextromethorphan/quinidine (Nuedexta) can be used for pseudobulbar affect (see Chapter 24 ). • The underlying cause of the cerebrovascular disease must also be evaluated and treated.
Top differential diagnoses	• Mixed dementia (vascular dementia or vascular cognitive impairment plus another neurodegenerative disease such as Alzheimer’s disease or Lewy body disease), Alzheimer’s disease, depression.

His medical history included diabetes mellitus type 2 and hypertension. His review of systems was notable for frequent urinary and occasional fecal incontinence. His neurological examination was notable for brisk reflexes throughout. He had bilateral Babinski responses. On the Montreal Cognitive Assessment (MoCA) he scored 23, missing points on the alternating number-letter connect-the-dots, clock hands, serial 7s, and delayed recall (although all the items he missed he recalled with category cues or multiple choice).

Prevalence, Prognosis, and Definition

Vascular dementia is dementia due to cerebrovascular disease (i.e., strokes) ( Fig. 6-1 ). When cerebrovascular disease causes cognitive dysfunction but not severe enough to lead to functional impairment, the term vascular cognitive impairment is used. Vascular cognitive impairment is a shorthand way of saying, “mild cognitive impairment due to cerebrovascular disease” ( Table 6-1 ).

TABLE 6-1

Comparison Between Vascular Dementia, Vascular Cognitive Impairment, Alzheimer’s Disease Dementia, and Mild Cognitive Impairment Due to Alzheimer’s Disease

	Vascular Dementia	Vascular Cognitive Impairment	Alzheimer’s Disease Dementia	Mild Cognitive Impairment due to Alzheimer’s Disease
Cognitive complaints by patient or family	Present	Present	Present	Present
Cognitive deficits	Present	Present, very mild	Present	Present, very mild
Functional impairment	Present	Absent	Present	Absent
Dementia	Present	Absent	Present	Absent
Likely underlying pathology	Cerebrovascular disease	Cerebrovascular disease	Alzheimer’s disease	Alzheimer’s disease
Deterioration over time	May occur, but may also remain stable	May occur, but may also remain stable	Always occurs	Occurs if diagnosis correct
FDA-approved treatment	None	None	Cholinesterase inhibitors, memantine	None
Recommended treatment	Cholinesterase inhibitors	Cholinesterase inhibitors	Cholinesterase inhibitors	Cholinesterase inhibitors
	Memantine if apathy	Memantine if apathy	Memantine if apathy
	SSRI if depression or anxiety	SSRI if depression or anxiety	SSRI if depression or anxiety	SSRI if depression or anxiety

The prevalence of vascular dementia and vascular cognitive impairment depends on how they are defined. If vascular dementia is defined such that patients with Alzheimer’s disease and other neurodegenerative diseases are excluded, then vascular dementia is a relatively small cause of memory loss and dementia, of the order of 5–10% of all dementias, depending upon the particular population (closer to 10% in US veterans, for example). We would describe such patients as having a “pure vascular dementia.” Like most older adults, the majority of patients with Alzheimer’s disease and other degenerative diseases (such as dementia with Lewy bodies) have some cerebrovascular disease, usually in the form of small vessel ischemic disease. If these patients were also included in the definition of vascular dementia, then the majority of patients with dementia would have vascular dementia or vascular cognitive impairment—along with another type of dementia.

We typically classify the cognitively impaired patient with cerebrovascular disease in one of the following ways. If the patient shows no signs of any other etiology of his or her cognitive impairment, we would describe him or her as having a “pure vascular dementia” (or “pure vascular cognitive impairment,” if not demented). If the patient has a neurodegenerative disease (such as Alzheimer’s) and he or she has the average amount of cerebrovascular disease that a non-demented, non-cognitively impaired older adult has, we would describe him or her as simply having that neurodegenerative disease (such as Alzheimer’s). If the patient has a neurodegenerative disease (such as Alzheimer’s) and he or she has a greater than average amount of cerebrovascular disease—such that it is highly likely that the cerebrovascular disease is making a significant contribution to the patient’s dementia—then we would describe him or her as having a “mixed dementia,” and would then further specify, for example, “a mixed dementia of Alzheimer’s disease plus vascular dementia” ( Fig. 6-2 ). Patients classified in this way with a mixed dementia of cerebrovascular disease plus a neurodegenerative disease probably make up 10–15% of all dementias.

Criteria

There are many published criteria for vascular dementia. The two that we find most helpful are those from the International Society for Vascular Behavioral and Cognitive Disorders (commonly known as VASCOG) and the DSM-5; they can be found below in Boxes 6-1 and 6-2 . (See Boxes 3-1 and 3-3 for DSM-5 criteria for Major and Mild Neurocognitive Disorder.) Both criteria include that:

•

The cognitive disorder can be major or mild
•

History, exam, and/or neuroimaging evidence of cerebrovascular events is required
•

Cognitive deficits in attention, processing speed, and frontal/executive function are common
•

A temporal relationship between cognitive deficits and cerebrovascular events is supportive.

Box 6-1

International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) Criteria for Vascular Cognitive Disorders

I

Criteria for Mild Cognitive Disorder and Dementia (or Major Cognitive Disorder)

Mild Cognitive Disorder

1.

Acquired decline from a documented or inferred previous level of performance in ≥1 cognitive domains (attention and processing speed, frontal/executive function, learning and memory, language, visuoconstructional-perceptual ability, praxis-gnosis-body schema, social cognition) as evidenced by the following:
- a.
  
  Concerns of a patient, knowledgeable informant, or a clinician, of mild levels of decline from a previous level of cognitive functioning, and
- b.
  
  Evidence of modest deficits (1 to 2 standard deviations below norms) on objective cognitive assessment based on a validated measure of neurocognitive function in ≥1 cognitive domains.
2.

The cognitive deficits are not sufficient to interfere with independence in instrumental activities of daily living, but greater effort, compensatory strategies, or accommodation may be required.

Dementia or Major Cognitive Disorder

1.

Evidence of substantial cognitive decline from a documented or inferred previous level of performance in ≥1 cognitive domains based on:
- a.
  
  Concerns of the patient, a knowledgeable informant, or the clinician, of significant decline in specific abilities; and
- b.
  
  Clear and significant deficits (≥2 standard deviations below the mean) in objective assessment based on a validated objective measure of neurocognitive function in ≥1 cognitive domains.
2.

The cognitive deficits are sufficient to interfere with independence in instrumental activities of daily living.

II

Evidence for Predominantly Vascular Etiology of Cognitive Impairment

1.

One of the following clinical features:
- a.
  
  The onset of the cognitive deficits is temporally related to ≥1 cerebrovascular events, as evidenced by one of the following:
  - 1)
    
    Documented history of a stroke, with cognitive decline temporally associated with the event
  - 2)
    
    Physical signs consistent with stroke.
- b.
  
  Evidence for decline is prominent in speed of information processing, complex attention, and/or frontal/executive functioning in the absence of history of a stroke or transient ischemic attack. One of the following features is additionally present:
  - 1)
    
    Early presence of a gait disturbance (small-step gait or marche à petits pas, or magnetic, apraxic-ataxic, or parkinsonian gait); this may also manifest as unsteadiness and frequent, unprovoked falls
  - 2)
    
    Early urinary frequency, urgency, and other urinary symptoms not explained by urologic disease
  - 3)
    
    Personality and mood changes: abulia, depression, or emotional incontinence.
2.

Presence of significant neuroimaging (MRI or CT) evidence of cerebrovascular disease (one of the following):
- a.
  
  One large vessel infarct is sufficient for Mild Vascular Cognitive Disorder, and ≥2 large vessel infarcts are generally necessary for Vascular Dementia(or Major Vascular Cognitive Disorder)
- b.
  
  An extensive or strategically placed single infarct, typically in the thalamus or basal ganglia may be sufficient for Vascular Dementia (or Major Vascular Cognitive Disorder)
- c.
  
  Multiple lacunar infarcts (>2) outside the brainstem; 1–2 lacunes may be sufficient if strategically placed or in combination with extensive white matter lesions
- d.
  
  Extensive and confluent white matter lesions
- e.
  
  Strategically placed intracerebral hemorrhage, or ≥2 intracerebral hemorrhages
- f.
  
  Combination of the above.

Exclusion Criteria (for Mild and Major Vascular Cognitive Disorder)

- a.
  
  History
  - 1)
    
    Early onset of memory deficit and progressive worsening of memory and other cognitive functions such as language, motor skills, and perception in the absence of corresponding focal lesions on brain imaging or history of vascular events
  - 2)
    
    Early and prominent parkinsonian features suggestive of Lewy body disease
  - 3)
    
    History strongly suggestive of another primary neurological disorder sufficient to explain the cognitive impairment.
- b.
  
  Neuroimaging
  - 1)
    
    Absent or minimal cerebrovascular lesions on CT or MRI.
- c.
  
  Other medical disorders severe enough to account for memory and related symptoms:
  - 1)
    
    Other disease of sufficient severity to cause cognitive impairment
  - 2)
    
    Major depression, with a temporal association between cognitive impairment and the likely onset of depression
  - 3)
    
    Toxic and metabolic abnormalities, all of which may require specific investigations.