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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 outcomes of clinically diagnosed VaD. Mixed type 1 revealed large infracts, whereas mixed type 2 predominantly exhibited SVD with microinfarction. Other included Lewy body disease, dementia, mild Parkinson disease and depression. AD Alzheimer’s disease
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Fig3: Pathological outcomes of clinically diagnosed VaD. Mixed type 1 revealed large infracts, whereas mixed type 2 predominantly exhibited SVD with microinfarction. Other included Lewy body disease, dementia, mild Parkinson disease and depression. AD Alzheimer’s disease

Mentions: Concurrent CVD is a common neuropathological finding in aged subjects with dementia and more common in AD than in other neurodegenerative disorders, especially in younger subjects. This is evident not only in samples from memory clinics we first evaluated over 20 years ago [136], but also in those from large multicentre studies [164]. In the National Alzheimer’s Coordinating Centre minimum data set sample of 4429 clinically diagnosed AD cases, the presence of CVD and any vascular pathology was reported to be 32 and 80 % respectively. Approximately, 20 % of these had lacunes and microinfarcts [164]. The admixture of CVD pathology and neurodegenerative changes particularly neurofibrillary and α-synuclein pathologies is even greater in elderly people within the community at large [29, 140, 157]. The co-occurrence of CVD lowers the threshold for dementia caused by a single neurodegenerative process. In one community-based sample, 38 % of dementia cases had mixed pathology, with both Alzheimer-type changes and vascular lesions, but ‘pure AD’ represented only 21–24 % of the cases [148]. WM lesions indicating ischaemic or oligaemic aetiology are also high in community-dwelling subjects by as much as 94 %, and this change is an independent substrate for dementia [50]. In addition, atherosclerosis in cerebral arteries and the circle of Willis [141, 187] is frequently present in AD. The commonest overlapping pathologies involve smaller cerebrovascular lesions rather than large infarcts [39] (Fig. 3). These include most features of SVD such as cortical infarcts, lacunes, diffuse and periventricular myelin loss, WM microvacuolation, microinfarcts, microhaemorrhages, arteriolosclerosis and focal and diffuse gliosis [10, 48, 173]. AD pathology was found to be three times greater in VaD cases with small (<15 mL) compared to large infarcts [10]. The findings also corroborate the importance of microvascular disease rather than large vessel disease as the critical substrate in VaD and AD.Fig. 3


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

Kalaria RN - Acta Neuropathol. (2016)

Pathological outcomes of clinically diagnosed VaD. Mixed type 1 revealed large infracts, whereas mixed type 2 predominantly exhibited SVD with microinfarction. Other included Lewy body disease, dementia, mild Parkinson disease and depression. AD Alzheimer’s disease
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Pathological outcomes of clinically diagnosed VaD. Mixed type 1 revealed large infracts, whereas mixed type 2 predominantly exhibited SVD with microinfarction. Other included Lewy body disease, dementia, mild Parkinson disease and depression. AD Alzheimer’s disease
Mentions: Concurrent CVD is a common neuropathological finding in aged subjects with dementia and more common in AD than in other neurodegenerative disorders, especially in younger subjects. This is evident not only in samples from memory clinics we first evaluated over 20 years ago [136], but also in those from large multicentre studies [164]. In the National Alzheimer’s Coordinating Centre minimum data set sample of 4429 clinically diagnosed AD cases, the presence of CVD and any vascular pathology was reported to be 32 and 80 % respectively. Approximately, 20 % of these had lacunes and microinfarcts [164]. The admixture of CVD pathology and neurodegenerative changes particularly neurofibrillary and α-synuclein pathologies is even greater in elderly people within the community at large [29, 140, 157]. The co-occurrence of CVD lowers the threshold for dementia caused by a single neurodegenerative process. In one community-based sample, 38 % of dementia cases had mixed pathology, with both Alzheimer-type changes and vascular lesions, but ‘pure AD’ represented only 21–24 % of the cases [148]. WM lesions indicating ischaemic or oligaemic aetiology are also high in community-dwelling subjects by as much as 94 %, and this change is an independent substrate for dementia [50]. In addition, atherosclerosis in cerebral arteries and the circle of Willis [141, 187] is frequently present in AD. The commonest overlapping pathologies involve smaller cerebrovascular lesions rather than large infarcts [39] (Fig. 3). These include most features of SVD such as cortical infarcts, lacunes, diffuse and periventricular myelin loss, WM microvacuolation, microinfarcts, microhaemorrhages, arteriolosclerosis and focal and diffuse gliosis [10, 48, 173]. AD pathology was found to be three times greater in VaD cases with small (<15 mL) compared to large infarcts [10]. The findings also corroborate the importance of microvascular disease rather than large vessel disease as the critical substrate in VaD and AD.Fig. 3

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