Brain amyloid β, cerebral small vessel disease, and cognition

Abstract

Objective:to evaluate the association between brain amyloid-beta (Aβ) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition in a memory clinic study.Methods:186 memory clinic individuals, diagnosed with no cognitive impairment (NCI), cognitive impairment no dementia (CIND), Alzheimer’s dementia (AD) or Vascular dementia (VaD) were included. Brain Aβ was measured by [11C]-PiB-PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing.Results:an increase in global SUVR is associated with a decrease in MMSE, in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND (P for interaction:.009), with an increase of the effect size of Aβ (β=-6.03(1.50), P<.001) compared to the model without the interaction term (β =-2.57(0.80), P =.002).Conclusion:higher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH, only in CIND. This suggests that Aβ and CSVD are independent processes with a possible synergistic effect between Aβ and WMH in individuals with CIND. There was no interaction effect between Aβ and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction.

Effects of white matter hyperintensities distribution and clustering on late-life cognitive impairment

“…Habes and colleagues (2018) recently showed that the increase in frontal PV-WMH precedes the accumulation of lesions at other locations, which might suggest that WMH progress from the periventricular to juxtacortical areas 50 . Given this, it is possible that the presence of WMH in the temporal lobe or juxtacortical areas, rather than being a specific pattern of distribution of WMH, might indicate that patients had a longer progression of cerebrovascular disease, probably accelerating Alzheimer’s disease (AD)-related pathology as amyloid beta accumulation (Aβ) 51 , 52 or hippocampal atrophy 53 . Similarly, age-related decline in free-recall neuropsychological tests have been shown to precede impairment in episodic memory function 54 , while the latter is relative preserved until advanced stages of cognitive impairment 55 .…”

Role of White Matter Hyperintensities and Related Risk Factors in Vascular Cognitive Impairment: A Review

“…Specifically, the association has been found between cerebral amyloid burden and WMHs located in the posterior periventricular regions and the splenium of the corpus callosum [56]. Also, in those with cognitive impairment but not dementia, a possible synergistic effect has been observed between cerebral amyloid burden and WMH in cases of worsening cognition [57]. However, whether amyloid pathology shows a causal link with WMH progression and is associated with eventual VCI remains unclear due to lack of data, although tau protein has been implicated in the association of WMHs with impairment of cognition.…”

Is Oxidative Stress the Link Between Cerebral Small Vessel Disease, Sleep Disruption, and Oligodendrocyte Dysfunction in the Onset of Alzheimer’s Disease?

“…Vascular dysfunction is integral to the AD etiology and pathophysiology, and it includes blood–brain barrier (BBB) impairment and hemodynamic dysfunction ( Klohs, 2020 ; Parodi-Rullán et al, 2020 ). CSVD also has a predictive effect on AD risk among the elderly people, and there are several epidemiological, genetic, and clinical studies related to both pathologies ( Kim et al, 2020 ; Saridin et al, 2020 ). However, whether CSVD is a cause or consequence of AD pathology still remains a controversial issue.…”