Proceedings from the Albert Charitable Trust Inaugural Workshop on white matter and cognition in aging

Abstract

This third in a series of vascular cognitive impairment (VCI) workshops, supported by "The Leo and Anne Albert Charitable Trust," was held from February 8 to 12 at the Omni Resort in Carlsbad, CA. This workshop followed the information gathered from the earlier two workshops suggesting that we focus more specifically on brain white matter in age-related cognitive impairment. The Scientific Program Committee (Frank Barone, Shawn Whitehead, Eric Smith, and Rod Corriveau) assembled translational, clinical, and basic scientists with unique expertise in acute and chronic white matter injury at the intersection of cerebrovascular and neurodegenerative etiologies. As in previous Albert Trust workshops, invited participants addressed key topics related to mechanisms of white matter injury, biomarkers of white matter injury, and interventions to prevent white matter injury and age-related cognitive decline. This report provides a synopsis of the presentations and discussions by the participants, including the existing knowledge gaps and the delineation of the next steps towards advancing our understanding of white matter injury and age-related cognitive decline. Workshop discussions and consensus resulted in action by The Albert Trust to (1) increase support from biannual to annual "White Matter and Cognition" workshops; (2) provide funding for two collaborative, novel research grants annually submitted by meeting participants; and(3) coordinate the formation of the "Albert Research Institute for White Matter and Cognition." This institute will fill a gap in white matter science, providing white matter and cognition communications, including annual updates from workshops and the literature and interconnecting with other Albert Trust scientific endeavors in cognition and dementia, and providing support for newly established collaborations between seasoned investigators and to the development of talented young investigators in the VCI-dementia (VCID) and white matter cognition arena.

Nicotinamide mononucleotide (NMN) supplementation promotes neurovascular rejuvenation in aged mice: transcriptional footprint of SIRT1 activation, mitochondrial protection, anti-inflammatory, and anti-apoptotic effects

“…We hope that our findings will facilitate future endeavors to uncover the mechanistic role of neurovascular NAD + depletion in brain aging and the pathogenesis of VCI. The recently appreciated complex role of NVU dysfunction (ranging from impaired neurovascular coupling to blood-brain barrier disruption) in neurodegenerative diseases and VCI supports the concept that pharmacological treatments, which maintain neurovascular health, promote brain health (Kisler et al 2017;Zlokovic 2010Zlokovic , 2011Csipo et al 2019a, b;de Montgolfier et al 2019;Farias Quipildor et al 2019;Fulop et al 2019;Sorond et al 2019;Sagare et al 2013). Potentially, NAD + booster treatments (e.g., in combination with STACs) could be harnessed for development of new pharmacological approaches for neurovascular protection for the prevention and treatment of VCI and neurodegenerative diseases in older adults.…”

White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer’s disease (AD) neuropathology: A hypothesis and review

“…How age predisposes to AD, however, has not been clear (Stahon et al, 2016). One possibility is that age-induced injury to white matter could be the primary reason (Liu et al, 2017;Chen et al, 2020;Sorond et al (2020)). Indeed, age and APOE-ε4 allele status affect myelin content in white matter of cognitively normal adults (Operto et al, 2019).…”

Assessment of the outer retina and choroid in white matter lesions participants using swept‐source optical coherence tomography

“…The presence of WMLs on radiologic scans increases the risk of cognitive decline and dementia (Miyao et al., 1992). Besides, recent reports (Levit et al., 2020; Sorond et al., 2020) have shown the importance of white matter integrity in the development of age‐related cognitive decline, and that neurovascular unit dysregulation and executive dysfunction often appear together WMLs. Thus, timely and effective approaches become critical as therapies are more likely to be successful in the early phase of the disease rather than the late phase.…”