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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

WM lesions visualised by conventional histopathological staining in a 69-year-old man diagnosed with vascular encephalopathy (and VaD). a >75 % stenosis in the internal carotid artery 8 mm above the bifurcation. The narrowed lumen (arrow) is seen. b Severe WM changes in the parietal lobe in this patient. Braak staging was graded as IV, but there were no neuritic or cored plaques. c Postmortem T2W magnetic resonance image of a formalin-fixed block from the parietal lobe. The area of hypersignal can be seen in the WM (asterisk). d H&E stained section from the block in c showing severe deep WM pallor in the area of hypertensity (asterisk). A small cortical infarct is also seen (arrow). Magnification bara 500 mm, b 400 μm, c 1 cm, d 500 μm
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Fig5: WM lesions visualised by conventional histopathological staining in a 69-year-old man diagnosed with vascular encephalopathy (and VaD). a >75 % stenosis in the internal carotid artery 8 mm above the bifurcation. The narrowed lumen (arrow) is seen. b Severe WM changes in the parietal lobe in this patient. Braak staging was graded as IV, but there were no neuritic or cored plaques. c Postmortem T2W magnetic resonance image of a formalin-fixed block from the parietal lobe. The area of hypersignal can be seen in the WM (asterisk). d H&E stained section from the block in c showing severe deep WM pallor in the area of hypertensity (asterisk). A small cortical infarct is also seen (arrow). Magnification bara 500 mm, b 400 μm, c 1 cm, d 500 μm

Mentions: White matter hyperintensities on T2-weighted MRI or leukoaraiosis as a decreased signal on computed tomography (CT) is a neuroimaging construct to describe diffuse and focal WM changes. Leukoariaosis predominantly has reference to vascular disease. It not only incorporates WM rarefaction, incomplete infarction, lacunar strokes, perivascular spacing and demyelination, but sometimes also axonal degeneration (Figs. 4 and 5). Both, areas of leukoaraiosis and zones outside the lesions show decreased vascular density indicating that leukoaraiosis appears as a generalised feature of CVD rather than being limited to the deep WM. This is consistent with the finding of an association of unstable carotid plaques with the number of WM lesions, suggesting a thromboembolic role in some patients with leukoaraiosis [5].Fig. 5


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

Kalaria RN - Acta Neuropathol. (2016)

WM lesions visualised by conventional histopathological staining in a 69-year-old man diagnosed with vascular encephalopathy (and VaD). a >75 % stenosis in the internal carotid artery 8 mm above the bifurcation. The narrowed lumen (arrow) is seen. b Severe WM changes in the parietal lobe in this patient. Braak staging was graded as IV, but there were no neuritic or cored plaques. c Postmortem T2W magnetic resonance image of a formalin-fixed block from the parietal lobe. The area of hypersignal can be seen in the WM (asterisk). d H&E stained section from the block in c showing severe deep WM pallor in the area of hypertensity (asterisk). A small cortical infarct is also seen (arrow). Magnification bara 500 mm, b 400 μm, c 1 cm, d 500 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: WM lesions visualised by conventional histopathological staining in a 69-year-old man diagnosed with vascular encephalopathy (and VaD). a >75 % stenosis in the internal carotid artery 8 mm above the bifurcation. The narrowed lumen (arrow) is seen. b Severe WM changes in the parietal lobe in this patient. Braak staging was graded as IV, but there were no neuritic or cored plaques. c Postmortem T2W magnetic resonance image of a formalin-fixed block from the parietal lobe. The area of hypersignal can be seen in the WM (asterisk). d H&E stained section from the block in c showing severe deep WM pallor in the area of hypertensity (asterisk). A small cortical infarct is also seen (arrow). Magnification bara 500 mm, b 400 μm, c 1 cm, d 500 μm
Mentions: White matter hyperintensities on T2-weighted MRI or leukoaraiosis as a decreased signal on computed tomography (CT) is a neuroimaging construct to describe diffuse and focal WM changes. Leukoariaosis predominantly has reference to vascular disease. It not only incorporates WM rarefaction, incomplete infarction, lacunar strokes, perivascular spacing and demyelination, but sometimes also axonal degeneration (Figs. 4 and 5). Both, areas of leukoaraiosis and zones outside the lesions show decreased vascular density indicating that leukoaraiosis appears as a generalised feature of CVD rather than being limited to the deep WM. This is consistent with the finding of an association of unstable carotid plaques with the number of WM lesions, suggesting a thromboembolic role in some patients with leukoaraiosis [5].Fig. 5

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