Neurovascular unit dysregulation, white matter disease, and executive dysfunction: the shared triad of vascular cognitive impairment and Alzheimer disease

Abstract

Executive dysfunction is the most important predictor for loss of independence in dementia. As executive function involves the coordination of distributed cerebral functions, executive function requires healthy white matter. However, white matter is highly vulnerable to cerebrovascular insults, with executive dysfunction being a core feature of vascular cognitive impairment (VCI). At the same time, cerebrovascular pathology, white matter disease, and executive dysfunction are all increasingly recognized as features of Alzheimer disease (AD). Recent studies have characterized the crucial role of glial cells in the pathological changes observed in both VCI and AD. In comorbid VCI and AD, the glial cells of the neurovascular unit (NVU) emerge as important therapeutic targets for the preservation of white matter integrity and executive function. Our synthesis from current research identifies dysregulation of the NVU, white matter disease, and executive dysfunction as a fundamental triad that is common to both VCI and AD. Further study of this triad will be critical for advancing the prevention and management of dementia.

Impaired cerebral autoregulation is associated with poststroke cognitive impairment

“…Consistent with our results, studies have reported that patients with lacunar infarction had impaired CA in bilateral hemispheres 32,33 . The possible mechanism behind this phenomenon is neurovascular unit dysfunction in small vessel disease, 34 which is consistent with the finding that VLF phase shift is the optimal CA index for predicting poststroke cognitive impairment. Patients with AD were found to have normal CA, 35 which is consistent with the lack of association between CA and lobar microbleeds observed in the current study.…”

CVN‐AD Alzheimer's mice show premature reduction in neurovascular coupling in response to spreading depression and anoxia compared to aged controls

“…Both brain glucose and oxygen could be measured with PET dynamic activation as a potential method to highlight patients for specific metabolic interventions 11 . Further, neurovascular coupling to a variety of activation paradigms may be tested in MCI and AD patients to understand the translation of these concepts to the clinical condition 28 . These could be tested with clinical activation including sensory or direct nerve stimulation.…”

Mapping the transcriptomic changes of endothelial compartment in human hippocampus across aging and mild cognitive impairment

“…However, the comprehension of brain vascular pathophysiology requires the understanding of their molecular basis. To achieve this goal, both the multifactorial nature of these diseases and the central concept of neurovascular unity (NVU) should be considered ( Takahashi, 2020 ; Levit et al, 2020 ). However, the complex biology behind the neurovascular brain pathology is still full of open questions.…”