Limits...
Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease.

Kalaria RN - Acta Neuropathol. (2016)

Bottom Line: Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered.Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of dementia associated with cerebral small vessel disease.Greater understanding of the neurochemical and molecular investigations is needed to better define microvascular disease and vascular substrates of dementia.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK. r.n.kalaria@ncl.ac.uk.

ABSTRACT
Vascular dementia (VaD) is recognised as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. The heterogeneity of cerebrovascular disease makes it challenging to elucidate the neuropathological substrates and mechanisms of VaD as well as vascular cognitive impairment (VCI). Consensus and accurate diagnosis of VaD relies on wide-ranging clinical, neuropsychometric and neuroimaging measures with subsequent pathological confirmation. Pathological diagnosis of suspected clinical VaD requires adequate postmortem brain sampling and rigorous assessment methods to identify important substrates. Factors that define the subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes. Atherosclerotic and cardioembolic diseases appear the most common substrates of vascular brain injury or infarction. Small vessel disease characterised by arteriolosclerosis and lacunar infarcts also causes cortical and subcortical microinfarcts, which appear to be the most robust substrates of cognitive impairment. Diffuse WM changes with loss of myelin and axonal abnormalities are common to almost all subtypes of VaD. Medial temporal lobe and hippocampal atrophy accompanied by variable hippocampal sclerosis are also features of VaD as they are of Alzheimer's disease. Recent observations suggest that there is a vascular basis for neuronal atrophy in both the temporal and frontal lobes in VaD that is entirely independent of any Alzheimer pathology. Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered. Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of dementia associated with cerebral small vessel disease. Greater understanding of the neurochemical and molecular investigations is needed to better define microvascular disease and vascular substrates of dementia. The investigation of relevant animal models would be valuable in exploring the pathogenesis as well as prevention of the vascular causes of cognitive impairment.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of different cerebrovascular pathologies associated with dementia. The proposed Newcastle categorisation includes six subtypes [90]. In all the above, the age of the vascular lesion(s) should correspond with the time when the disease began. The post-stroke survivors are usually included in subtypes I–III. While these may not be different from other published subtypes [84], they are practical and simple to use. Cases with extensive WM disease in the absence of significant other features are included under SVD. *Subtype I may result from large vessel occlusion (atherothromboembolism), artery to artery embolism or cardioembolism. Subtype II usually involves descriptions of arteriosclerosis, lipohyalinosis and hypertensive, arteriosclerotic, amyloid or collagen angiopathy. Subtypes I, II and V may result from aneurysms, arterial dissections, arteriovenous malformations and various forms of arteritis (vasculitis). AD Alzheimer’s disease, CH cerebral haemorrhage, CVD cerebrovascular disease, MI myocardial infarction, MID multi-infarct dementia, LVD large vessel disease, SIVD subcortical ischaemic vascular dementia, SVD small vessel disease, VCI vascular cognitive impairment, VaD vascular dementia
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835512&req=5

Fig1: Schematic diagram of different cerebrovascular pathologies associated with dementia. The proposed Newcastle categorisation includes six subtypes [90]. In all the above, the age of the vascular lesion(s) should correspond with the time when the disease began. The post-stroke survivors are usually included in subtypes I–III. While these may not be different from other published subtypes [84], they are practical and simple to use. Cases with extensive WM disease in the absence of significant other features are included under SVD. *Subtype I may result from large vessel occlusion (atherothromboembolism), artery to artery embolism or cardioembolism. Subtype II usually involves descriptions of arteriosclerosis, lipohyalinosis and hypertensive, arteriosclerotic, amyloid or collagen angiopathy. Subtypes I, II and V may result from aneurysms, arterial dissections, arteriovenous malformations and various forms of arteritis (vasculitis). AD Alzheimer’s disease, CH cerebral haemorrhage, CVD cerebrovascular disease, MI myocardial infarction, MID multi-infarct dementia, LVD large vessel disease, SIVD subcortical ischaemic vascular dementia, SVD small vessel disease, VCI vascular cognitive impairment, VaD vascular dementia

Mentions: Neuropathological diagnosis of VaD should be based on the absence of a primary neurodegenerative disease known to cause dementia and the presence of cerebrovascular pathology that defines one or more of the VaD subtypes (Table 1). These would also include dementia among post-stroke survivors who fulfill the NINDS-AIREN criteria [144] for probable VaD. Stroke survivors with mild cognitive impairment or VCI [118] may also have sufficient pathology for neuropathological diagnosis of VaD [4]. A proposal for the neuropathological diagnostic evaluation of VaD was previously published by the Newcastle investigators (Fig. 1). According to these criteria, there are two neuropathological diagnostic groups: probable VaD is based on the exclusion of a primary neurodegenerative disease known to cause dementia plus the presence of cerebrovascular pathology that defines one or more of the VaD subtypes. Possible VaD is designated when the brain contains vascular pathology that does not fulfill the criteria for one of the subtypes, but where no other explanation for dementia is found. Post-stroke survivors are often classed as subtypes I–III. Cases with extensive WM disease in the absence of other significant pathologies are included under SVD.Fig. 1


Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer's disease.

Kalaria RN - Acta Neuropathol. (2016)

Schematic diagram of different cerebrovascular pathologies associated with dementia. The proposed Newcastle categorisation includes six subtypes [90]. In all the above, the age of the vascular lesion(s) should correspond with the time when the disease began. The post-stroke survivors are usually included in subtypes I–III. While these may not be different from other published subtypes [84], they are practical and simple to use. Cases with extensive WM disease in the absence of significant other features are included under SVD. *Subtype I may result from large vessel occlusion (atherothromboembolism), artery to artery embolism or cardioembolism. Subtype II usually involves descriptions of arteriosclerosis, lipohyalinosis and hypertensive, arteriosclerotic, amyloid or collagen angiopathy. Subtypes I, II and V may result from aneurysms, arterial dissections, arteriovenous malformations and various forms of arteritis (vasculitis). AD Alzheimer’s disease, CH cerebral haemorrhage, CVD cerebrovascular disease, MI myocardial infarction, MID multi-infarct dementia, LVD large vessel disease, SIVD subcortical ischaemic vascular dementia, SVD small vessel disease, VCI vascular cognitive impairment, VaD vascular dementia
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835512&req=5

Fig1: Schematic diagram of different cerebrovascular pathologies associated with dementia. The proposed Newcastle categorisation includes six subtypes [90]. In all the above, the age of the vascular lesion(s) should correspond with the time when the disease began. The post-stroke survivors are usually included in subtypes I–III. While these may not be different from other published subtypes [84], they are practical and simple to use. Cases with extensive WM disease in the absence of significant other features are included under SVD. *Subtype I may result from large vessel occlusion (atherothromboembolism), artery to artery embolism or cardioembolism. Subtype II usually involves descriptions of arteriosclerosis, lipohyalinosis and hypertensive, arteriosclerotic, amyloid or collagen angiopathy. Subtypes I, II and V may result from aneurysms, arterial dissections, arteriovenous malformations and various forms of arteritis (vasculitis). AD Alzheimer’s disease, CH cerebral haemorrhage, CVD cerebrovascular disease, MI myocardial infarction, MID multi-infarct dementia, LVD large vessel disease, SIVD subcortical ischaemic vascular dementia, SVD small vessel disease, VCI vascular cognitive impairment, VaD vascular dementia
Mentions: Neuropathological diagnosis of VaD should be based on the absence of a primary neurodegenerative disease known to cause dementia and the presence of cerebrovascular pathology that defines one or more of the VaD subtypes (Table 1). These would also include dementia among post-stroke survivors who fulfill the NINDS-AIREN criteria [144] for probable VaD. Stroke survivors with mild cognitive impairment or VCI [118] may also have sufficient pathology for neuropathological diagnosis of VaD [4]. A proposal for the neuropathological diagnostic evaluation of VaD was previously published by the Newcastle investigators (Fig. 1). According to these criteria, there are two neuropathological diagnostic groups: probable VaD is based on the exclusion of a primary neurodegenerative disease known to cause dementia plus the presence of cerebrovascular pathology that defines one or more of the VaD subtypes. Possible VaD is designated when the brain contains vascular pathology that does not fulfill the criteria for one of the subtypes, but where no other explanation for dementia is found. Post-stroke survivors are often classed as subtypes I–III. Cases with extensive WM disease in the absence of other significant pathologies are included under SVD.Fig. 1

Bottom Line: Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered.Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of dementia associated with cerebral small vessel disease.Greater understanding of the neurochemical and molecular investigations is needed to better define microvascular disease and vascular substrates of dementia.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK. r.n.kalaria@ncl.ac.uk.

ABSTRACT
Vascular dementia (VaD) is recognised as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. The heterogeneity of cerebrovascular disease makes it challenging to elucidate the neuropathological substrates and mechanisms of VaD as well as vascular cognitive impairment (VCI). Consensus and accurate diagnosis of VaD relies on wide-ranging clinical, neuropsychometric and neuroimaging measures with subsequent pathological confirmation. Pathological diagnosis of suspected clinical VaD requires adequate postmortem brain sampling and rigorous assessment methods to identify important substrates. Factors that define the subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes. Atherosclerotic and cardioembolic diseases appear the most common substrates of vascular brain injury or infarction. Small vessel disease characterised by arteriolosclerosis and lacunar infarcts also causes cortical and subcortical microinfarcts, which appear to be the most robust substrates of cognitive impairment. Diffuse WM changes with loss of myelin and axonal abnormalities are common to almost all subtypes of VaD. Medial temporal lobe and hippocampal atrophy accompanied by variable hippocampal sclerosis are also features of VaD as they are of Alzheimer's disease. Recent observations suggest that there is a vascular basis for neuronal atrophy in both the temporal and frontal lobes in VaD that is entirely independent of any Alzheimer pathology. Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered. Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of dementia associated with cerebral small vessel disease. Greater understanding of the neurochemical and molecular investigations is needed to better define microvascular disease and vascular substrates of dementia. The investigation of relevant animal models would be valuable in exploring the pathogenesis as well as prevention of the vascular causes of cognitive impairment.

No MeSH data available.


Related in: MedlinePlus