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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

Sampling of postmortem brain tissue for assessing vascular pathology. Coronal blocks from one hemisphere (rostral to caudal) of the cerebrum for an ‘ideal’ sample for neuropathological assessment. In Newcastle, large sections are taken as indicated by the pink and green blocks identified by the letters. A minimum sample constituting four to six large blocks including S, Y/W, F/J, G/H, AB/AD and AL can be reliably used to determine the burden of vascular pathology [39]
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Fig2: Sampling of postmortem brain tissue for assessing vascular pathology. Coronal blocks from one hemisphere (rostral to caudal) of the cerebrum for an ‘ideal’ sample for neuropathological assessment. In Newcastle, large sections are taken as indicated by the pink and green blocks identified by the letters. A minimum sample constituting four to six large blocks including S, Y/W, F/J, G/H, AB/AD and AL can be reliably used to determine the burden of vascular pathology [39]

Mentions: Gross external examination of the brain at autopsy is extremely useful for a quick indication of the presence of cerebrovascular pathology (Table 2). As is widely practiced, the brain from CVD cases is cut in the coronal plane throughout. This is irrespective of whether fresh samples are dissected for freezing at autopsy or the brain is immersion fixed for later sectioning. In Newcastle, brains from CVD cases are sliced fresh in the coronal plane and then alternate sections from each hemisphere are retained as fixed or frozen material, which is deposited in the Newcastle Brain Tissue Resource. While unconventional, it has been the normal practice for the past 30 years in Newcastle to sample large sections (average size 6 × 5 cm) for better appreciation of pathology, but this is not necessarily the case in many laboratories (Fig. 2).Fig. 2


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

Kalaria RN - Acta Neuropathol. (2016)

Sampling of postmortem brain tissue for assessing vascular pathology. Coronal blocks from one hemisphere (rostral to caudal) of the cerebrum for an ‘ideal’ sample for neuropathological assessment. In Newcastle, large sections are taken as indicated by the pink and green blocks identified by the letters. A minimum sample constituting four to six large blocks including S, Y/W, F/J, G/H, AB/AD and AL can be reliably used to determine the burden of vascular pathology [39]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Sampling of postmortem brain tissue for assessing vascular pathology. Coronal blocks from one hemisphere (rostral to caudal) of the cerebrum for an ‘ideal’ sample for neuropathological assessment. In Newcastle, large sections are taken as indicated by the pink and green blocks identified by the letters. A minimum sample constituting four to six large blocks including S, Y/W, F/J, G/H, AB/AD and AL can be reliably used to determine the burden of vascular pathology [39]
Mentions: Gross external examination of the brain at autopsy is extremely useful for a quick indication of the presence of cerebrovascular pathology (Table 2). As is widely practiced, the brain from CVD cases is cut in the coronal plane throughout. This is irrespective of whether fresh samples are dissected for freezing at autopsy or the brain is immersion fixed for later sectioning. In Newcastle, brains from CVD cases are sliced fresh in the coronal plane and then alternate sections from each hemisphere are retained as fixed or frozen material, which is deposited in the Newcastle Brain Tissue Resource. While unconventional, it has been the normal practice for the past 30 years in Newcastle to sample large sections (average size 6 × 5 cm) for better appreciation of pathology, but this is not necessarily the case in many laboratories (Fig. 2).Fig. 2

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