Aetiology
Vascular dementia is the final common endpoint of many varied vascular pathologies. The aetiology is also often multifactorial, with several vascular diseases leading to dementia.[10] Vascular pathologies include the following.
Infarction: can be due to embolisation, thrombosis, lacunar infarction, hypoxia, hypoglycaemia, or ischaemia. Micro-infarcts identified on MRI appear to be common in patients with dementia.[16][17]
Leukoaraiosis: a disease of white matter also called subcortical leukoencephalopathy.
Haemorrhage: either large parenchymal haemorrhages or multiple small haemorrhages.
Post-stroke cognitive impairment is common, particularly in the first year, and ranges from mild to severe. Although reversible in some cases early on after stroke, up to one third of individuals develop dementia within 5 years.[18]
Some risk factors for cerebrovascular disease are also associated with an increased risk of Alzheimer’s disease. These include raised systolic blood pressure, hypercholesterolaemia, diabetes, and air pollution.[19][20][21] History of hospital-treated infection is also associated with onset of dementia in later life - vascular dementia more so than Alzheimer’s - and is not specific to particular types of infection, suggesting that dementia risk is driven by general inflammation rather than specific microbes.[22] A Swedish study found that herpes simplex virus infection doubles the risk of all-cause dementia in older adults, while there is no such correlation with cytomegalovirus infection.[23]
Pathophysiology
Infarction
Multiple large infarcts, once they reach a certain volume and affect a large enough number of individual brain regions, will exhaust the brain's compensatory mechanisms and lead to dementia.[24]
Small infarcts in strategic areas such as the basal ganglia and thalamus can also lead to dementia with only a small volume of brain having been infarcted.[7] Small infarcts <1.5 cm in size are called lacunar infarctions and are caused by arteriosclerosis of the small irrigating superficial and deep penetrating arteries and arterioles. The underlying cause is thought to be hypertension. The basal ganglia, thalamus, pons, internal capsule, and deep white matter areas are maximally affected.[25]
Leukoaraiosis
This causes white matter pallor to the naked eye. Microscopically, loss of axons, myelin, and oligodendrocytes is noted. There is perivascular tissue loss and dilation of the perivascular spaces. There is damage to the capillaries with breakdown of the blood-brain barrier and protein leakage.[8] Frank infarction is rare; ischaemia is hypothesised to be the cause. Vigorous vascular pulsation has been implicated in the causation of the white matter disease.[26]
Haemorrhage
Large parenchymal haemorrhages centred in the basal ganglia are often secondary to hypertension, whereas multiple small haemorrhages occurring in the cortex and white matter are usually secondary to amyloid angiopathy.[27] The angiopathy is due to amyloid beta protein, which is deposited in the small arteriolar walls and renders them prone to rupture.
Mixed dementia
Alzheimer’s dementia and vascular dementia are not mutually exclusive. Each appears to act synergistically with the other. When they co-exist, a patient with dementia is affected to a greater degree than if they had only a single pathology.[28]
Classification
NINDS-CSN harmonisation standards[1]
Macrovascular disease
Multiple large cortical infarcts
Border-zone/watershed infarcts
Small strategic infarcts: for example, bilateral thalamic strokes
Microvascular disease
Multiple lacunar infarcts, particularly basal ganglia
Leukoaraiosis-extensive white matter disease (subcortical leukoencephalopathy).
Haemorrhage
Major parenchyma haemorrhage
Cerebral amyloid angiopathy.
Mixed vascular parenchymal pathology
Mixed dementia types: for example, AD-vascular dementia.
Diagnostic and Statistical Manual of Mental Disorders, 5th ed., text revision (DSM-5-TR) classification of major and mild neurocognitive disorders[2][3]
DSM-5-TR defines major and mild neurocognitive disorders as being due to:
Alzheimer's disease
Frontotemporal degeneration
Lewy body disease
Vascular disease
Traumatic brain injury
Substance/medication use
HIV infection
Prion disease
Parkinson's disease
Huntington's disease
Another medical condition
Multiple aetiologies
Unknown aetiology.
Severity is defined for major neurocognitive disorders as mild, moderate, or severe; and the presence or absence of behavioural and psychological symptoms is also specified.
Specific criteria relating to vascular neurocognitive disorder are given in Diagnostic criteria.
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