Alterations of the cerebral cortex in sporadic small vessel disease: A systematic review of in vivo MRI data

Wilisch‐Neumann

Neuropathology Appl Neurobio

et al. 2019

Invited Review: The spectrum of age-related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathiesDeep perforator arteriopathy (DPA) and cerebral amyloid angiopathy (CAA) are the commonest known cerebral small vessel diseases (CSVD), which cause ischaemic stroke, intracebral haemorrhage (ICH) and vascular cognitive impairment (VCI). While thus far mainly considered as separate entities, we here propose that DPA and CAA share similarities, overlap and interact, so that 'pure' DPA or CAA are extremes along a continuum of age-related small vessel pathologies. We suggest blood-brain barrier (BBB) breakdown, endothelial damage and impaired perivascular b-amyloid (Ab) drainage are hallmark common mechanisms connecting DPA and CAA. We also suggest a need for new biomarkers (e.g. high-resolution imaging) to deepen understanding of the complex relationships between DPA and CAA.

Section: Neuroimaging Biomarkers Of Sporadic Csvdmentioning

confidence: 90%

Section: Neuroimaging Biomarkers Of Sporadic Csvdmentioning

confidence: 92%

Invited Review: The spectrum of age‐related small vessel diseases: potential overlap and interactions of amyloid and nonamyloid vasculopathies

Wilisch‐Neumann

Neuropathology Appl Neurobio

et al. 2019

Neuropathology Appl Neurobio

“…Regional atrophy of pyramidal cells without other characteristics of neurodegenerative disease has been described and associated with clinical dementia, and it has been proposed that the underlying cause is vascular . In addition, imaging studies have indicated a correlation between cortical thinning and WMD but have been criticized for not taking the possible co‐occurrence of neurodegenerative disease into account .…”

Section: Discussionmentioning

confidence: 99%

A cortical microvascular structure in vascular dementia, Alzheimer's disease, frontotemporal lobar degeneration and nondemented controls: a sign of angiogenesis due to brain ischaemia?

Olofsson

Englund

2019

AimsWe observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a ‘raspberry’, referring to its appearance under a bright‐field microscope. We hypothesized that raspberries form through angiogenesis due to some form of brain ischaemia or hypoperfusion. The aims of this study were to quantify raspberry frequency within the cerebral cortex according to diagnosis (vascular dementia, Alzheimer's disease, frontotemporal lobar degeneration and nondemented controls) and brain regions (frontal, temporal, parietal and occipital cortices, regardless of diagnosis).Materials and methodsIn each of 10 age‐matched subjects per group, a 20‐mm section of the cerebral cortex was examined in haematoxylin‐and‐eosin‐stained sections of the frontal, temporal and parietal, and/or occipital lobes. Tests were performed to validate the haematoxylin‐and‐eosin‐based identification of relative differences between the groups, and to investigate inter‐rater variability.ResultsRaspberry frequency was highest in subjects with vascular dementia, followed by those with frontotemporal lobar degeneration, Alzheimer's disease and last, nondemented controls. The frequency of raspberries in subjects with vascular dementia differed from that of all other groups at a statistically significant level. In the cerebral lobes, there was a statistically significant difference between the frontal and occipital cortices.ConclusionsWe believe the results support the hypothesis that raspberries are a sign of angiogenesis in the adult brain. It is pertinent to discuss possible proangiogenic stimuli, including brain ischaemia (such as mild hypoperfusion due to a combination of small vessel disease and transient hypotension), neuroinflammation and protein pathology.

“…Numerous studies identified MRI markers of SVD (lacunes, white matter hyperintensities, cerebral microbleeds, silent infarcts, white matter changes, global cerebral atrophy, medial-temporal lobe atrophy) as determinants of VaD (18,19). Vascular lesions traditionally attributed to VCI comprise subcortical areas of the brain, especially subfrontal white matter circuits, strategic areas of single infarction such as the dominant thalamus or angular gyrus, deep frontal areas and the left hemisphere, and bilateral brain infarcts or volume-driven cortical-subcortical infarctions reaching a critical threshold of tissue loss or injury (20). Recently, enlargements of perivascular spaces were identified as MRI markers of SVD.…”

Section: Imaging Morphologic Substrates Of Svdmentioning

confidence: 99%

The Additional Value of PET in the Assessment of Cerebral Small Vessel Disease

Heiss

2018

J Nucl Med

The diagnosis of cerebral small vessel disease (SVD) is difficult because there is no consensus on clinical criteria, and therefore imaging is important for diagnosis. Most patients undergo brain imaging by CT, which is able to detect ischemic strokes, hemorrhages, and brain atrophy and may also indicate white matter changes. MRI remains the key neuroimaging modality and is preferred to CT in vascular cognitive impairment (VCI) because it has higher sensitivity and specificity for detecting pathologic changes. These modalities for imaging morphology permit detection of vascular lesions traditionally attributed to VCI in subcortical areas of the brain, single infarction or lacunes in strategic areas (thalamus or angular gyrus), or large cortical-subcortical lesions reaching a critical threshold of tissue loss. In SVD, multiple punctuate or confluent lesions can be seen in the white matter by MRI and were called leukoaraiosis. Another major neuroimaging finding of SVD in VCI are microhemorrhages. However, whereas CT and MRI are able to detect morphologic lesions, these modalities cannot determine functional consequences of the underlying pathologic changes. PET can support the clinical diagnosis by visualizing cerebral functions in typically affected brain regions. In SVD, F-FDG PET can clearly differentiate scattered areas of focal cortical and subcortical hypometabolism that differ from the typical metabolic pattern seen in Alzheimer dementia (AD) with marked hypometabolism affecting the association areas. Additional PET tracers can further support the diagnosis of a type of dementia and also yield information on the underlying pathophysiology.