The main causes of vascular dementia are cerebrovascular disorders and their risk factors. The prevalent cerebrovascular disorders include large artery disease (artery-to-artery embolism, occlusion of an extra- or intracranial artery), cardiac embolic events, small-vessel disease (lacunar infarcts, ischaemic white-matter lesions) and haemodynamic mechanisms.^{(13, 14 and 15)} Less frequent causes include specific arteriopathies including cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADACIL) and cerebral amyloid angiopathy (CAA), haemorrhage (intracranial haemorrhage, subarachnoidal haemorrhage), haematological factors, venous disease, and hereditary disorders. There may be as yet undiscovered causes.

In most patients diagnosed with vascular dementia, several aetiological factors are involved. However, the roles these factors play have not been identified in detail, and it is not certain which of these mechanisms distinguish vascular dementia from cerebrovascular disease without dementia.^{(4,5,7,16,17)}

Risk factors for vascular dementia can be divided into vascular factors (e.g. arterial hypertension, atrial fibrillation, myocardial infarction, coronary heart disease, diabetes, generalized atherosclerosis, lipid abnormalities, smoking), demographic factors (e.g. age, education), genetic factors (e.g. family history, individual genetic features), and stroke-related factors (e.g. type of cerebrovascular disease, site and size of stroke).^(18,19) Hypoxic ischaemic events (cardiac arrhythmias, congestive heart failure, myocardial infarction, seizures, pneumonia) may be an important risk factor for incident dementia in patients with stroke.⁽²⁰⁾

Vascular dementia is related to both ischaemic and non-ischaemic changes in the brain.^(4,5,13,14) The ischaemic lesions include arterial territorial infarct, distal field (watershed) infarct, lacunar infarct, ischaemic white-matter lesions, and incomplete ischaemic injury. Incomplete ischaemic injury incorporates laminar necrosis, focal gliosis, granular atrophy, and incomplete white-matter infarction.^(21,22) In addition, both focal (around the ischaemic lesion) and remote (disconnection, diaschisis) functional ischaemic changes relate to vascular dementia, and the volume of functionally inactive tissue exceeds that of focal ischaemic lesions in vascular dementia.⁽²³⁾ Limitation in current clinical methods have hampered the detection of both incomplete ischaemic injury and functional ischaemic changes related to vascular dementia. Atrophy is the non-ischaemic factor related to vascular dementia. However, there are no methods to distinguish between ischaemic and degenerative causes of atrophy clinically.

Work on the relationship between brain lesions and cognition in vascular dementia has used varying definitions and measures of cognitive impairment, varying techniques to reveal brain changes, and varying criteria for the selection of patients.⁽¹⁷⁾

CT and magnetic resonance imaging (MRI) studies on vascular dementia have shown that bilateral ischaemic lesions are important.^(4,5,7,17) Some studies emphasize deep infarcts in the frontal and limbic areas, while others report cortical lesions especially in the temporal and parietal areas. There is disagreement about the number and volume of the infarcts, as well as the extent and location of atrophy. Diffuse and extensive white-matter lesions have been suggested as an important factor leading to functional disconnection of cortical brain areas. Some general conclusions on brain lesions in vascular dementia may be drawn.

The extent to which pathological changes in the brain cause, compound, or only coexist with the vascular dementia syndrome is still uncertain. The vascular changes in the brain can be the main cause of cognitive impairment (as assumed in vascular dementia^(24,25)), they can contribute to the clinical picture of other dementia syndromes including Alzheimer’s disease (AD),^(7,26) or they may be coincidental. The occurrence of infarcts may cause an earlier presentation of clinical symptoms in a brain in which there is existing and progressive Alzheimer’s disease pathology.⁽²⁶⁾

It is not certain which are the critical changes in the brain leading to the clinical picture of vascular dementia. The syndrome has been related to the volume of brain infarcts (with a critical threshold), the number of infarcts, the site of infarcts (bilateral, in strategic cortical or subcortical, or affecting white matter), to other ischaemic factors (incomplete ischaemic injury, delayed neuronal death, functional changes), to the atrophic changes (origin, location, extent), and finally to the additive effects of other pathologies
(Alzheimer’s disease, Lewy body dementia, frontal lobe dementias). But it is uncertain which type, extent, side, site, and tempo of vascular lesions in the brain, and which combination with other pathologies, relate to vascular dementia.^{(4, 5 and 6,13)}

Vascular dementia has been divided into subtypes on the basis of clinical, radiological, and neuropathological features. It is uncertain whether these subtypes are distinct disorders, with separate pathological and clinical features, and responses to therapy.⁽²⁷⁾ If homogenous subtypes could be identified the comparability of research studies would be greater and multicentre studies easier.⁽²⁸⁾

The subtypes of vascular dementia included in most classifications include multi-infarct dementia (cortical lesions), small-vessel dementia or subcortical ischaemic vascular disease and dementia (SIVD) (subcortical deep lesions), and strategic infarct dementia.^{(12,14,27,29, 30, 31, 32 and 33)} Many include also hypoperfusion dementia.^{(12,14,30,34)} Further suggested subtypes include haemorrhagic dementia, hereditary vascular dementia, and combined or mixed dementia (Alzheimer’s disease with cerebrovascular disease).

DSM-IV⁽³⁵⁾ does not specify subtypes. ICD-10⁽³⁶⁾ includes six subtypes (acute onset, multi-infarct, subcortical, mixed cortical and subcortical, other, and unspecified). The NINDS-AIREN criteria⁽³⁰⁾ include, without detailed description, cortical vascular dementia, subcortical vascular dementia, Binswanger’s disease, and thalamic dementia. In addition separate research criteria for subcortical vascular dementia, the SIVD, have been proposed.⁽³⁷⁾

Multi-infarct dementia or cortical vascular dementia, and small-vessel dementia or subcortical vascular dementia are the two common subtypes, although their frequencies vary in different series.^(12,14,31)

Cortical vascular dementia relates to large-vessel disease, cardiac embolic events, and hypoperfusion. Infarcts are predominantly in the cortical and corticosubcortical arterial territories, and their distal fields (watershed). Typical clinical features are lateralized sensorimotor changes and the abrupt onset of cognitive impairment and aphasia.⁽³¹⁾ A combination of different cortical neuropsychological syndromes has been suggested to occur in cortical vascular dementia.⁽³⁸⁾

Subcortical vascular dementia, small-vessel dementia, the SIVD^(33,37) incorporates the entities ‘lacunar state’ and ‘Binswanger’s disease’. It relates to small-vessel disease and hypoperfusion, with predominately lacunar infarcts, focal and diffuse ischaemic white-matter lesions, and incomplete ischaemic injury.^{(31,33,37, 38 and 39)} Clinically, small-vessel dementia is characterized by pure motor hemiparesis, bulbar signs, dysarthria, depression, and emotional lability, and especially deficits in executive functioning.^{(38, 39, 40 and 41)}

Since the 1970s several clinical criteria for vascular dementia have been published.^(11,42,43) The most widely used include those in DSM-IV,⁽³⁵⁾ ICD-10,⁽³⁶⁾ and NINDS-AIREN.⁽³⁰⁾

The two cardinal elements of any clinical criteria for vascular dementia are the definition of the cognitive syndrome⁽⁴⁴⁾ and the definition of the cause.^(11,43,45) All clinical criteria are consensus criteria, derived neither from prospective community-based studies on vascular factors affecting the cognition, nor on detailed natural histories.^{(28,30,42,43,46)} All these criteria are based on the concept of ischaemic infarcts. They are designed to have high specificity, but have been poorly validated.^(42,46) An important consequence of the different definitions of the dementia syndrome,^(9,44) and the vascular cause,^(10,11) is that the different diagnostic criteria identify different populations.

The DSM-IV definition of vascular dementia (Table 4.1.8.1) requires focal neurological signs and symptoms or laboratory evidence of focal neurological damage clinically judged to be related to the disturbance.⁽³⁵⁾ The course is specified by sudden cognitive and functional losses. The DSM-IV criteria do not detail brain imaging requirements. The DSM-IV definition of vascular dementia is reasonably broad and lacks detailed clinical and radiological guidelines.

The ICD-10 criteria⁽³⁶⁾ (Table 4.1.8.2) require unequal distribution of cognitive deficits, focal signs as evidence of focal brain damage, and significant cerebrovascular disease judged to be aetiologically related to the dementia. The criteria do not detail brain imaging requirements. The ICD-10 criteria specify six subtypes of vascular dementia (Table 4.1.8.3). The ICD-10 criteria for vascular dementia have been shown to be highly selective and only some of those fulfilling the general criteria for ICD-10 vascular dementia
can be classified into one of the subtypes.^(11,45) The shortcoming of these criteria include lack of detailed guidelines (e.g. of unequal cognitive deficits and changes on neuroimaging), lack of aetiological criteria, and heterogeneity.^(11,45)