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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Acta+Neuropathol
2016 ; 131
(5
): 659-85
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Neuropathological diagnosis of vascular cognitive impairment and vascular
dementia with implications for Alzheimer s disease
#MMPMID27062261
Kalaria RN
Acta Neuropathol
2016[May]; 131
(5
): 659-85
PMID27062261
show ga
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.