Review of Cerebral Microangiopathy and Alzheimer’s Disease: Relation between White Matter Hyperintensities and Microbleeds

Abstract

Although Alzheimer’s disease (AD) is basically considered to be a neurodegenerative disorder, cerebrovascular disease is also involved. The role of vascular risk factors and vascular disease in the progression of AD remains incompletely understood. With the development of brain MRI, it is now possible to detect small-vessel disease, whose prevalence and severity increase with age. The first types of small-vessel disease to be described were white matter hyperintensities (WMHs). More recently, small areas of signal loss on T₂*-weighted images, also called microbleeds (MBs), have been reported. Cerebral MBs are focal deposits of hemosiderin that indicate prior microhemorrhages around small vessels, related to either ruptured atherosclerotic microvessels or amyloid angiopathy. Consequently, using brain MRI for the detection of microangiopathy may prove useful to improve our understanding of the impact of the vascular burden in AD pathology. The relationship between microangiopathy and the clinical course of AD or the conversion of mild cognitive impairment to AD remains questionable in terms of cognitive or affective symptoms, particularly if we consider MBs.

Prolonged diet induced obesity has minimal effects towards brain pathology in mouse model of cerebral amyloid angiopathy: Implications for studying obesity–brain interactions in mice

“…Localized changes in microglial reactivity, and a selective elevation in IL-6 (but not IL-1 or TNF-α) was observed in CAA mice in response to DIO. The lack of gross DIO effects towards Aβ pathogenesis is surprisingly consistent with a number of studies in the literature [32–36], and points to a need to carefully consider the current experimental limitations in studying the effects of DIO on the brain. The potential for ceiling effects in Aβ pathogenesis within the various mouse models, the lack of consistency for DIO based experimentation, and the current experimental limitations for DIO in mice to fully replicate metabolic dysfunction present in human obesity, are discussed.…”

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

“…Why some AD subjects decline more rapidly than others is not clearly understood. Several factors have been suggested to contribute to disease progression [94,99]: demographic factors (level of education, age), clinical features (extrapyramidal signs, age of onset of the disease, nutritional status) [100,101,102,103], presence of psychotic symptoms [104], cholinesterase inhibitor treatment [105,106], genetic factors [apolipoprotein E (APOE) ε4 allele] [97,107,108], cerebrovascular disease and vascular risk factors [109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125]. Even though several demographic, clinical or genetic factors have been proposed for explaining the rate of decline in AD, they do not fully explain the variability observed in the different rates of clinical progression.…”

Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients

“…Cerebral microbleeds (CMBs) are considered a marker of cerebral small vessel disease, which can be visualized as small, rounded, homogenous and hypointense lesions on T2*-weighted gradient-recalled echo (T2*-GRE) or susceptibility-weighted imaging (SWI)-magnetic resonance imaging (MRI), corresponding to small perivascular hemosiderin deposits from leakage through cerebral small vessels [1,2]. The locations of CMBs probably represent different underlying pathologies.…”