When people get older, the risk of cerebrovascular disease increases. Approximately 70% of individuals over the age of 70 exhibit evidence of vascular lesions on MRI-scans. These lesions can have different clinical profiles. Some small lesions can result in little to no cognitive impairment and other lesions are so severe, that they result in clinical dementia. Vascular cognitive impairment was introduced as a term to describe all forms of cognitive impairment causes by cerebrovascular disease. The type of impairment associated with vascular cognitive impairment depends on the location and amount of damaged tissue. This in turn influences the severity of behavioural, cognitive and psychiatric features. Early identification of vascular dementia is important, because many of the risk factors for vascular disease are modifiable. At the mildest end, with vascular cognitive impairment is called a vascular cognitive impairment no dementia (VCIND). At the severe end, with vascular cognitive impairment is referred to as vascular dementia and it is one of the more common types of dementia among older adults after Alzheimer’s Disease. Approximately one-third of individuals will develop dementia within one year after a stroke. When a stroke affects a very large vessel, or is strategically located, the result is likely consistent with the concept of dementia due to stroke. Clinical symptoms with associated with stroke are very variable and depend upon the area impacted. Impairment due to large vessel or strategic stroke is most commonly tied to the concept of vascular dementia, but it is not the most common expression of the disease. Vascular dementia has a more insidious onset and a slow and gradual decline. Mixed dementia between vascular cognitive impairment and vascular dementia is common, but it is controversial in the field.

Clinical presentation

With vascular cognitive impairment, clinical preconceptions of disease expression and progression are not realized, because heterogeneity is the rule. Patterns of abrupt onset and stepwise decline in function are less common than a slow and progressive disease course. With this disease, executive dysfunction may predominate, but the neuropsychological presentation will be driven by the extent of diffuse and focal vascular injuries in the brain.

Vascular cognitive impairment, no dementia

VCIND refers to vascular lesions that can be seen on MRI, but that cause impairment too mild to impact activities of daily living. The most common types that can be visualised on MRI are lacunes (small cerebrospinal filled cavities in the white matter) and subcortical hyperintensities (vascular-related damage). It is not uncommon for a person to have this type of vascular damage and show normal neuropsychological abilities. VCIND may be a prodromal stage for vascular dementia, VaD. Because of this, modifiable risk factors may be important in reducing the progression of the disease. One study showed that half of the VCIND cases progressed to dementia over a 5-year period in time. People who have VCIND and frontal white matter hyperintensities are less likely to revert back to normal cognitive function after 1 year as compared to people with VCIND who do not have frontal white matter hyperintesities. Modifiable risk factors may play an important role in determining the progression of VCIND to VaD. The current pharmacological treatment options for VaD are relatively ineffective at arresting disease progression, so there is a need for early identification and clinical intervention. There is not a consistent neuropsychological profile that is predictive of advancement from VCIND to VaD, but people with VCIND often display poor performance on tests of cognitive flexibility, psychomotor speed and learning. VCIND may also increase the incidence of depression, but it is not known if vascular damage is the cause of depression or a result of the deficits.

Vascular dementia

VaD results from extensive white matter lesions and lacunar infarcts due to small vessel disease, it can also result from one or more strokes to the main cerebral arteries, or the combination of the two. The most common impaired domains of function in VaD are learning, delayed memory, executive function, with intact recognition memory. The deficits in executive function are most typically found on tests of verbal fluency, response inhibition and mental flexibility. Episodic memory deficits are found on tests of recall and list learning. Recognition may stay intact if the structures of the medial temporal lobe are not damaged. Depression is the most common behavioural feature associated with stroke. 20% of people with strokes also exhibit depression. The strongest predictor of depression is reduction in the ability to carry out activities of daily living. However, this may be confounded by stroke severity. Increased depression is associated with greater cognitive impairment and increased mortality. Depression can’t explain the cognitive deficits found in patients with VaD. There are a couple of VaD criteria proposed. The most used criteria is memory deficit. The criteria for VaD from the DSM are:

1. Multiple deficits manifested by both

   1. Memory impairment

   2. At least one of the following:

      • Apraxia: motor activity impairment

      • Aphasia: language disturbance

      • Disturbance in executive functions (planning, organizing)

      • Agnosia: not recognising objects, despite intact sensory function

2. The deficits just mentioned cause impairment in occupational and social functioning and the functioning must show a decline from previous functioning

3. Focal neurological signs and symptoms or laboratory evidence for cerebrovascular disease

4. The deficits must not occur exclusively during the occurrence of a delirium

Risk factors for VCI

There are a couple of variables associated with increased risk for stroke. Strokes can occur in younger people (with sickle cell anemia), but they are most common among older people. The greatest risk factor associated with VCI is age. Other unmodifiable risk factors for stroke are male sex, atrial fibrillation, weight, race (African American) and ethnicity (Latino). There are also a couple of deterministic genetic factors that increase the risk of vascular disease. One of these is cerebral autosomal dominant arteriopathy with subcortical infarcts leukoencephalopathy (CADASIL). CADASIL is a rare autosomal disease and it is associated with a Notch3 defect that causes infarcts in the deep white matter, brain stem and basal ganglia. The average onset of a stroke is 45 years, but many individuals with CADASIL will experience migraine with aura with an average onset at age 30 years. People with CADASIL develop dementia by the sixth decade of life and they die by the seventh decade. The cognitive deficits of CADASIL patients impact organizational abilities, executive functions and attention. A susceptibility gene for vascular disease is angiotensinogen. This gene is involved with the development of subcortical ischemic disease. Cerebrovascular disease is the underlying cause of VCI, so the risk factors related to the development of VCI overlap with those related to cardiovascular disease. The improvement of risk factors underlying overall cardiovascular health lowers the risk of stroke. Studies have shown that stopping with smoking and lowering of hypertension result in reduced stroke risk in advanced age.

Differential diagnosis

When a clinician evaluates older adults for VCI, he/she may considerate other diagnoses. Some of these are Alzheimer’s Disease, Lewy body dementia, frontotemporal dementias and normal pressure hydrocephalus (NPH). NPH is quite similar to VCI, as both conditions share frontal symptoms, but NPH more frequently includes urinary urgency and gait disturbance. When these two are present, the likelihood of NPH as the appropriate diagnosis increases. Frontotemporal dementia presents with more unique symptoms than VCI, like aphasia or personality abnormalities. The age of onset for VCI is often older than what is typical for frontotemporal dementia. It is difficult for the clinician to rule out Alzheimer’s Disease. First, clinicians thought that the neuropsychological patterns of Alzheimer’s Disease and VCI and the decline of these were disease specific, but this position has been challenged. Autopsy shows that AD and vascular neuropathology frequently coexist. This means that many patients exhibit some degree of shares disease presentation during life. It is still not clear whether both conditions develop independently or whether one condition develops first, followed by the other.

Clinical evaluation

The model of vascular-mediate brain injury has evolved more than other neurodegenerative conditions over the last few decades. Beliefs about the course of decline, the neuropsychological pattern and the utility of MRI-defined vascular burden have shifted the approach and accuracy of the neuropsychological evaluation. The clinical evaluation should follow a patient-oriented approach. A clinician also needs personal, medical and neuropsychological information.

Interviews

The clinical interview is important for the assessment for vascular disease. Many patients have good insight into their cognitive deficits, but not all patients have full insight. Patients need to pay attention in order to describe their symptoms. Often, patients will confuse concepts or misinterpret the MRI report regarding cortical versus subcortical vascular disease. The access to medical records will clarify these issues, but some clinicians work in independent practice and the records may arrive after the patient has been evaluated. During the interview, a clinician can also observe language skills and potential aphasic abnormalities. The clinician can also see if the patients can recall information correctly. Sometimes patients may describe memory failure as a tip of the tongue phenomena, rather than outright amnesic failure, but during the interview, the clinician can see whether this is the case or not. During the interview, the clinician can also extract apathy and mood constructs from the patient.

Clinicians have difficulty to differentiate between a progressive and stepwise decline. The VCI literature has characterized the decline in physical and cognitive status associated with stroke as stepwise, while the insidious and progressive decline is part of Alzheimer’s Disease. When the partner or family describes a repetitive pattern of sharp decline followed by stabilization, the stepwise pattern was confirmed and vascular etiology would be considered more likely than a diagnosis of AD. This description of decline is appropriate for many infarcts, but the pattern does not hold for small vessel disease. Clinicians should not rely on the course of decline as a pathogenic sign of vascular disease and they need neuropsychological data and neuroimaging results.

Neuropsychological assessment

Some screening measures, like the mini-mental state exam, lack sensitivity to vascular-related impairments. The Montreal Cognitive Assessment (MoCA) was introduced to provide more coverage of executive processes in the screening of dementia. The MoCA is not specifically developed for VCI and it is unclear whether the task demands capture mild to moderate cognitive impairments associated with cerebrovascular disease in a good way. A couple of years ago it was suggested that a brief 30-min and a more comprehensive 60-min neuropsychological battery for VCI should be done. The 30-min battery is limited to psychomotor speed, verbal memory and verbal fluency. The 60-min battery represents all major cognitive systems like attention, working memory, processing speed, language and mood. For memory, it is critical to use measures that capture learning efficacy across trials, recognition and delayed retention. This can help to differentiate between AD and VCI. It is also recommended to measure both letter and category fluency, because people with VCI score poorer on letter fluency, while people with AD score poorer on category fluency.

Neuroimaging

Sometimes, it is tempting for clinicians to rely too heavily on neuropsychological data alone to determine the etiology of cognitive impairment. It will be the most problematic to the clinician in the case of VCI. However, when there is no obvious data present of neuropsychological impairment for VCI, it is important that neuroimaging results are integrated into the case conceptualization to reach a more whole diagnosis. The neuroimaging abnormalities that are associated with a stroke can be identified on high-powered MRI, using a fluid-attenuated inversion recovery (FLAIR) scan. Vascular disease on these images is characterized by lacunes in white and subcortical grey matter. Neuropsychologists are often not trained to review films independently, so the degree of vascular burden must be gleaned from the radiologist’s report. However, this has some problems, because radiologists do not use standard metric systems for determining the level of pathologic burden as neuropsychologists do. Cerebrovascular disease is common among the general population after age 65 years. So, this may cause some difficulties for the MRI interpretation, because there might be some vascular burden to be seen on the MRI-scan, but this might not be sufficient enough the account for the cognitive difficulties.