White matter degeneration in vascular and other ageing‐related dementias

  title={White matter degeneration in vascular and other ageing‐related dementias},
  author={Yoshiki Hase and Karen Horsburgh and Masafumi Ihara and Raj N. Kalaria},
  journal={Journal of Neurochemistry},
Advances in neuroimaging have enabled greater understanding of the progression of cerebral degenerative processes associated with ageing‐related dementias. Leukoaraiosis or rarefied white matter (WM) originally described on computed tomography is one of the most prominent changes which occurs in older age. White matter hyperintensities (WMH) evident on magnetic resonance imaging have become commonplace to describe WM changes in relation to cognitive dysfunction, types of stroke injury, cerebral… 
White matter capillaries in vascular and neurodegenerative dementias
The key finding indicates that WM capillaries are wider compared to those in the overlying neocortex in controls but they dilate further during dementia pathogenesis, which reflects compensatory changes to retain WM perfusion and integrity during hypoperfusive states in ageing-related dementias.
Cerebral Small Vessel Disease in Sporadic and Familial Alzheimer Disease
Loss of capillary pericytes and the blood–brain barrier in white matter in poststroke and vascular dementias and Alzheimer’s disease
It is indicated that deep WM pericytes are decreased across different dementias including PSD, VaD, Mixed and AD, and downregulation of pericyte numbers were correlated with PDGFR‐β reactivity in the WM.
Loss with ageing but preservation of frontal cortical capillary pericytes in post-stroke dementia, vascular dementia and Alzheimer’s disease
There is differential regulation of capillary pericytes in the frontal lobe between the cortex and white matter in ageing-related dementias, and capillary length densities identified by the endothelial marker glucose transporter 1 or COL4 were not different across the dementias compared to older controls.
White matter abnormalities are key components of cerebrovascular disease impacting cognitive decline
Though there is mechanistic heterogeneity in the cerebrovascular disease markers measured on MRI, these changes can be grouped into three components and together explain variability in cognitive performance equivalent to the impact of amyloidosis on cognition.
Role of White Matter Hyperintensities and Related Risk Factors in Vascular Cognitive Impairment: A Review
The status of research on the features of WMHs related to VCI, as well as mediators associated with bothWMHs and VCI are reviewed, and potential treatment strategies for the prevention and intervention in WMHS associated with VCI is summarized.
Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes
  • W. Zeng, Yaojing Chen, Zhanjun Zhang
  • Psychology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2019
Memory is the primary domain to be affected by WMH, and the effect may potentially be influenced by tract-specific WM abnormalities, which might be the critical stage predicting a future decline in cognition.
Small vessel disease pathological changes in neurodegenerative and vascular dementias concomitant with autonomic dysfunction
The findings suggest greater SVD pathological changes occur in the elderly diagnosed with neurodegenerative dementias including DLB and who develop autonomic dysfunction, and propose dysautonomia promotes chronic cerebral hypoperfusion to impact upon aging‐related neurodegenersative disorders and characterize their end‐stage clinical syndromes.
Neurovascular Alterations in Vascular Dementia: Emphasis on Risk Factors
The review summarizes the current knowledge related to the pathological mechanisms linking neurovascular impairments associated with stroke, cSVD, and vascular risk factors with a particular emphasis on air pollution, to VaD etiology and progression and discusses the major challenges to fully elucidate the pathobiology of VaD.


Gliovascular Disruption and Cognitive Deficits in a Mouse Model with Features of Small Vessel Disease
  • P. Holland, J. Searcy, K. Horsburgh
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2015
Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood–brain barrier alterations, and gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies.
Molecular disorganization of axons adjacent to human lacunar infarcts.
The degree of white matter injury associated with cerebral microvascular disease extends well beyond what can be identified using imaging techniques and that an improved understanding of the neurobiology in these regions can drive new therapeutic strategies for this disease entity.
Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations
Pathological substrates of WMH are heterogeneous in nature and severity, which may partly explain the weak clinicoradiological associations found in SVD.
Microglial activation in white matter lesions and nonlesional white matter of ageing brains
A difference in pathogenesis is suggested between these lesion‐types: the ramified, activated microglia associated with PVL may reflect immune activation resulting from disruption of the blood brain barrier, while the microglias within DSCL may reflect an innate, amoeboid phagocytic phenotype.
Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease
  • R. Kalaria
  • Medicine, Psychology
    Acta Neuropathologica
  • 2016
New 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.
Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer’s disease, and dementia with Lewy bodies
It is suggested that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration.
White Matter Lesions in an Unselected Cohort of the Elderly: Molecular Pathology Suggests Origin From Chronic Hypoperfusion Injury
A hypoxic environment within MRI WMLs appears to be a common feature of the aging brain, and persistent HIF expression may result from failure of normal adaptive mechanisms.
Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in white matter lesions in Alzheimer's disease
The results imply that regressive changes in astrocytes and glial apoptosis are, to some extent, associated with white matter lesions, particularly of the temporal lobe in AD brains.
Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia
The results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.