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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

CAA and infarcts in a 92-year-old woman with memory loss, confusional state and disorientation. CT on admission showed infarction in the right posterior parieto-occipital region. Small lacunar infarct in the posterior aspect of the left corona radiata, probable area of cortical infarction in the left occipital lobe. a Lobar haemorrhage in the frontal lobe. b Macroscopical cortical infarcts in both right and left occipital lobes. c, d Cortical and subarachnoidal arterioles showing thickened homogenous eosinophilic walls. Inset in c, two strongly stained eosinophilic vessels. e Aβ immunohistochemistry shows extensive subarachnoidal and cortical amyloid angiopathy. f A cortical microinfarct with haemosiderin. There were numerous microinfarcts in the frontal, parietal and occipital cortices. Subject only showed sparse cored and diffuse senile plaques and Braak stage II for neurofibrillary pathology. Magnification bara, b 1 cm, c–f 100 μm
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Fig6: CAA and infarcts in a 92-year-old woman with memory loss, confusional state and disorientation. CT on admission showed infarction in the right posterior parieto-occipital region. Small lacunar infarct in the posterior aspect of the left corona radiata, probable area of cortical infarction in the left occipital lobe. a Lobar haemorrhage in the frontal lobe. b Macroscopical cortical infarcts in both right and left occipital lobes. c, d Cortical and subarachnoidal arterioles showing thickened homogenous eosinophilic walls. Inset in c, two strongly stained eosinophilic vessels. e Aβ immunohistochemistry shows extensive subarachnoidal and cortical amyloid angiopathy. f A cortical microinfarct with haemosiderin. There were numerous microinfarcts in the frontal, parietal and occipital cortices. Subject only showed sparse cored and diffuse senile plaques and Braak stage II for neurofibrillary pathology. Magnification bara, b 1 cm, c–f 100 μm

Mentions: In addition to microinfarction in the subcortical structures, it appears increasingly important that multiple cortical areas of microinfarction are associated with subcortical VaD or SVD (Fig. 4). Thus, these lesions should be taken into account when defining the neuropathological criteria. Cortical microinfarcts are increased in the presence of CAA [121] (Fig. 6). In a recent study, cortical microinfarcts were frequently detected in AD and associated with CAA, but rarely observed in subcortical VaD linked to SVD [120, 159]. Microinfarcts in the cerebral cortex associated with severe CAA may be the primary pathological substrate in a significant proportion of VaD cases [74]. Cortical microinfarcts and to lesser extent periventricular demyelination were significantly associated with cognitive decline in individuals at high risk for dementia [63]. It is proposed the changes in hemodynamics, e.g. hypotension and atherosclerosis may play a role in the genesis of cortical watershed microinfarcts.Fig. 6


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

Kalaria RN - Acta Neuropathol. (2016)

CAA and infarcts in a 92-year-old woman with memory loss, confusional state and disorientation. CT on admission showed infarction in the right posterior parieto-occipital region. Small lacunar infarct in the posterior aspect of the left corona radiata, probable area of cortical infarction in the left occipital lobe. a Lobar haemorrhage in the frontal lobe. b Macroscopical cortical infarcts in both right and left occipital lobes. c, d Cortical and subarachnoidal arterioles showing thickened homogenous eosinophilic walls. Inset in c, two strongly stained eosinophilic vessels. e Aβ immunohistochemistry shows extensive subarachnoidal and cortical amyloid angiopathy. f A cortical microinfarct with haemosiderin. There were numerous microinfarcts in the frontal, parietal and occipital cortices. Subject only showed sparse cored and diffuse senile plaques and Braak stage II for neurofibrillary pathology. Magnification bara, b 1 cm, c–f 100 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig6: CAA and infarcts in a 92-year-old woman with memory loss, confusional state and disorientation. CT on admission showed infarction in the right posterior parieto-occipital region. Small lacunar infarct in the posterior aspect of the left corona radiata, probable area of cortical infarction in the left occipital lobe. a Lobar haemorrhage in the frontal lobe. b Macroscopical cortical infarcts in both right and left occipital lobes. c, d Cortical and subarachnoidal arterioles showing thickened homogenous eosinophilic walls. Inset in c, two strongly stained eosinophilic vessels. e Aβ immunohistochemistry shows extensive subarachnoidal and cortical amyloid angiopathy. f A cortical microinfarct with haemosiderin. There were numerous microinfarcts in the frontal, parietal and occipital cortices. Subject only showed sparse cored and diffuse senile plaques and Braak stage II for neurofibrillary pathology. Magnification bara, b 1 cm, c–f 100 μm
Mentions: In addition to microinfarction in the subcortical structures, it appears increasingly important that multiple cortical areas of microinfarction are associated with subcortical VaD or SVD (Fig. 4). Thus, these lesions should be taken into account when defining the neuropathological criteria. Cortical microinfarcts are increased in the presence of CAA [121] (Fig. 6). In a recent study, cortical microinfarcts were frequently detected in AD and associated with CAA, but rarely observed in subcortical VaD linked to SVD [120, 159]. Microinfarcts in the cerebral cortex associated with severe CAA may be the primary pathological substrate in a significant proportion of VaD cases [74]. Cortical microinfarcts and to lesser extent periventricular demyelination were significantly associated with cognitive decline in individuals at high risk for dementia [63]. It is proposed the changes in hemodynamics, e.g. hypotension and atherosclerosis may play a role in the genesis of cortical watershed microinfarcts.Fig. 6

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