Associations between white matter lesions, cerebrovascular risk factors, and low CSF Aβ42

Stenset, Vidar; Johnsen, Lisbeth; Kocot, D.; Negaard, Anne; Skinningsrud, Anders; Gulbrandsen, P.; Wallin, Anders; Fladby, Tormod

doi:10.1212/01.wnl.0000234030.77831.5a

Cited by 41 publications

(33 citation statements)

References 126 publications

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“…The current findings are in line with our early work establishing associations between low CSF Aβ 42 and WMHs, and also with our recently published data using MRI diffusion parameters to study WMH tissue integrity (19, 49). The latter data imply impaired microstructural integrity in WMHs in the presence of amyloid dysmetabolism, suggesting more pronounced oligodendroglial and axonal damage in the presence of amyloid pathology (19).…”

Section: Discussionsupporting

confidence: 92%

Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities

et al. 2016

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect gray matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease. WM glucose delivery and metabolism may have implications for local tissue integrity, and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) may be helpful to assess neuroglial and axonal function in WM. Hypothesizing that affection of oligodendroglia will be associated with loss of glucose uptake, we aimed to investigate glucose metabolism in magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) and normal-appearing WM in patients with and without evidence of amyloid plaques. Subjects with mild cognitive impairment or subjective cognitive decline were included and dichotomized according to pathological (Aβ+) or normal (Aβ−) concentrations of cerebrospinal fluid amyloid-β 1–42. A total of 50 subjects were included, of whom 30 subjects were classified as Aβ(+) and 20 subjects as Aβ(−). All subjects were assessed with MRI and FDG-PET. FDG-PET images were corrected for effects of partial voluming and normalized to cerebellar WM, before determining WMH FDG-uptake. Although there were no significant differences between the groups in terms of age, WMH volume, number of individual WMHs, or WMH distribution, we found significantly lower (p = 0.021) FDG-uptake in WMHs in Aβ(+) subjects (mean = 0.662, SD = 0.113) compared to Aβ(−) subjects (mean = 0.596, SD = 0.073). There were no significant group differences in the FDG-uptake in normal-appearing WM. Similar results were obtained without correction for effects of partial voluming. Our findings add to the evidence for a link between Aβ dysmetabolism and WM pathology in AD.

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Section: Discussionsupporting

confidence: 92%

Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities

et al. 2016

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“…Other authors have reported significant associations between WMH severity and amyloid burden measured in cerebrospinal fluid 50 . Here, we did not see a reliable difference between PIB positive and PIB negative individuals in overall WMH burden, which may be explained partially by the small sample size.…”

Section: Commentmentioning

confidence: 88%

White Matter Hyperintensities and Cerebral Amyloidosis

Provenzano¹,

Muraskin²,

Tosto³

et al. 2013

JAMA Neurol

167

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“…53 Microscopically, Ab accumulates around perivascular cells and affects the neurovascular unit (vascular and perivascular cells, glia, and neurons). Microvascular changes in AD and vascular cognitive impairment (VCI) include hyaline degradation, thickening of capillary basement membrane and reduction in numbers of capillaries, thereby also affecting the function of the blood-brain barrier.…”

Section: Discussionmentioning

confidence: 99%

White matter hyperintensity microstructure in amyloid dysmetabolism

Kalheim

Bjørnerud

Fladby

et al. 2016

J Cereb Blood Flow Metab

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Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N ¼ 51), dichotomized according to pathological or normal levels of amyloid-b peptide (Ab 42 ) in cerebrospinal fluid (CSF). Thirtyone subjects with low CSF Ab 42 (Abþ) and 20 subjects with normal CSF Ab 42 (AbÀ) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in Abþ relative to AbÀ; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.

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Associations between white matter lesions, cerebrovascular risk factors, and low CSF Aβ42

Cited by 41 publications

References 126 publications

Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities

Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities

White Matter Hyperintensities and Cerebral Amyloidosis

White matter hyperintensity microstructure in amyloid dysmetabolism

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