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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

Pathological features associated with SVD in VaD. Panels show examples of lacunes, small infarcts and microinfarcts. a Typical cavitated lacunar lesions (arrow) in the putamen of a 65-year-old man. b WM attenuation in the medial temporal lobe, but sparing of U fibres. Section from an 80-year-old man with vascular and neurofibrillary pathology. c, d Cerebral microvessels with variable hyalinosis, perivascular rarefaction, microinfarcts and perivascular spaces in two different cases. Moderate gliosis in the surrounding region is also evident in the case in c. d Perivascular dilatation (or spacing) in the WM (arrow). Magnification bara 1 cm, b 500 μm, c, d 100 μm
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Fig4: Pathological features associated with SVD in VaD. Panels show examples of lacunes, small infarcts and microinfarcts. a Typical cavitated lacunar lesions (arrow) in the putamen of a 65-year-old man. b WM attenuation in the medial temporal lobe, but sparing of U fibres. Section from an 80-year-old man with vascular and neurofibrillary pathology. c, d Cerebral microvessels with variable hyalinosis, perivascular rarefaction, microinfarcts and perivascular spaces in two different cases. Moderate gliosis in the surrounding region is also evident in the case in c. d Perivascular dilatation (or spacing) in the WM (arrow). Magnification bara 1 cm, b 500 μm, c, d 100 μm

Mentions: SVD entails fibroid necrosis, hyalinisation of vessels, expansion of the perivascular space and pallor of adjacent perivascular myelin, with associated astrocytic gliosis (Fig. 4). The smaller vessels of the brain including intracerebral end arteries and arterioles undergo progressive age-related changes [99], which alter perfusion and cause lacunar infarcts (cystic lesions generally <1 cm) and microinfarcts. The arteriolar changes range from wall thickening by hyalinosis, reduction or increment of the intima to severe arteriolosclerosis and fibroid necrosis. Arteriolosclerotic changes likely promote loss of elasticity to dilate and constrict in response to variations of systemic blood pressure or auto-regulation, which in turn causes fluctuations in blood flow response and changes in tissue perfusion. The deep cerebral structures and WM would be rendered most vulnerable, because the vessels are end arteries almost devoid of anastomoses. Small vessel pathology could also lead to oedema and damage of the blood–brain barrier (BBB) with chronic leakage of fluid and macromolecules in the WM [61, 78, 175]. Microvascular disease may also be associated with degrees of inflammation including the presence of lymphocytes or macrophages localised on blood vessels (and not necessarily a function of brain ischaemia). In the oldest SVD subjects, there may also often be evidence of remote haemorrhage in the form of perivascular hemosiderin [39].Fig. 4


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

Kalaria RN - Acta Neuropathol. (2016)

Pathological features associated with SVD in VaD. Panels show examples of lacunes, small infarcts and microinfarcts. a Typical cavitated lacunar lesions (arrow) in the putamen of a 65-year-old man. b WM attenuation in the medial temporal lobe, but sparing of U fibres. Section from an 80-year-old man with vascular and neurofibrillary pathology. c, d Cerebral microvessels with variable hyalinosis, perivascular rarefaction, microinfarcts and perivascular spaces in two different cases. Moderate gliosis in the surrounding region is also evident in the case in c. d Perivascular dilatation (or spacing) in the WM (arrow). Magnification bara 1 cm, b 500 μm, c, d 100 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Pathological features associated with SVD in VaD. Panels show examples of lacunes, small infarcts and microinfarcts. a Typical cavitated lacunar lesions (arrow) in the putamen of a 65-year-old man. b WM attenuation in the medial temporal lobe, but sparing of U fibres. Section from an 80-year-old man with vascular and neurofibrillary pathology. c, d Cerebral microvessels with variable hyalinosis, perivascular rarefaction, microinfarcts and perivascular spaces in two different cases. Moderate gliosis in the surrounding region is also evident in the case in c. d Perivascular dilatation (or spacing) in the WM (arrow). Magnification bara 1 cm, b 500 μm, c, d 100 μm
Mentions: SVD entails fibroid necrosis, hyalinisation of vessels, expansion of the perivascular space and pallor of adjacent perivascular myelin, with associated astrocytic gliosis (Fig. 4). The smaller vessels of the brain including intracerebral end arteries and arterioles undergo progressive age-related changes [99], which alter perfusion and cause lacunar infarcts (cystic lesions generally <1 cm) and microinfarcts. The arteriolar changes range from wall thickening by hyalinosis, reduction or increment of the intima to severe arteriolosclerosis and fibroid necrosis. Arteriolosclerotic changes likely promote loss of elasticity to dilate and constrict in response to variations of systemic blood pressure or auto-regulation, which in turn causes fluctuations in blood flow response and changes in tissue perfusion. The deep cerebral structures and WM would be rendered most vulnerable, because the vessels are end arteries almost devoid of anastomoses. Small vessel pathology could also lead to oedema and damage of the blood–brain barrier (BBB) with chronic leakage of fluid and macromolecules in the WM [61, 78, 175]. Microvascular disease may also be associated with degrees of inflammation including the presence of lymphocytes or macrophages localised on blood vessels (and not necessarily a function of brain ischaemia). In the oldest SVD subjects, there may also often be evidence of remote haemorrhage in the form of perivascular hemosiderin [39].Fig. 4

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