Vascular cognitive impairment and dementia: An early career researcher perspective

Abstract

The field of vascular contributions to cognitive impairment and dementia (VCID) is evolving rapidly. Research in VCID encompasses topics aiming to understand, prevent, and treat the detrimental effects of vascular disease burden in the human brain. In this perspective piece, early career researchers (ECRs) in the field provide an overview of VCID, discuss past and present efforts, and highlight priorities for future research. We emphasize the following critical points as the field progresses: (a) consolidate existing neuroimaging and fluid biomarkers, and establish their utility for pharmacological and non-pharmacological interventions; (b) develop new biomarkers, and new non-clinical models that better recapitulate vascular pathologies; (c) amplify access to emerging biomarker and imaging techniques; (d) validate findings from previous investigations in diverse populations, including those at higher risk of cognitive impairment (e.g., Black, Hispanic, and Indigenous populations); and (e) conduct randomized controlled trials within diverse populations with well-characterized vascular pathologies emphasizing clinically meaningful outcomes.

Keywords: VCID; early career researcher; vascular cognitive impairment; vascular dementia.

FIGURE 1

A conceptual model for vascular contributions to cognitive impairment and dementia (VCID). Note: This conceptual model highlights direct and indirect mechanisms in the causative chain of events yielding brain injury, ultimately leading to vascular cognitive impairment and dementia

FIGURE 2

Vascular contributions to cognitive impairment and dementia (VCID) publication trends over time based on a July 13, 2021, PubMed search through December 31, 2020. Note: (A) Number of publications per year based on a full search using the following terms: ((“vascular contributions to cognitive impairment and dementia”) OR ((vascular) AND ((cognitive impairment) OR (dementia)))) OR ((vascular) AND (mild cognitive impairment)). (B) Number of publications per year based on searching specifically for “(“vascular contributions to cognitive impairment and dementia”) OR (VCID)”

FIGURE 3

Emerging neuroimaging techniques in human and animal models. Note: (A) Myelin water fraction maps used to image in vivo myelin content in the human brain. Warmer regions indicate greater degree of myelination. In comparison are maps from two individuals with varying degrees of white matter lesion burden, courtesy of Dr. Teresa Liu‐Ambrose (The University of British Columbia). B, Time‐of‐flight angiography used to visualize small arteries that appear as thin thread‐like areas of flow‐related contrast in the human brain. C, Susceptibility‐weighted image used to visualize small veins in the human brain; (B) and (C) were adapted from Jorgensen et al. and replicated with permission. Images were acquired without the use of any contrast agents at 7T using the Tic Tac Toe Radiofrequency Coil System (http://rf‐research‐facility.engineering.pitt.edu/). Images were provided by Dr. Tamer Ibrahim (University of Pittsburgh). D, 3D reconstruction of a wild‐type mouse using three‐photon microscopy, the blood vessels are labeled with a 2.5% fluorescein isothiocyanate (FITC)‐dextran (red). Selected z‐stacks labeled with 2.5% FITC‐dextran (blood vessels; red) and third‐harmonic generation (THG) (myelinated axons; blue) labeled at 200 μm (upper panel) and the white matter at 800 μm (lower panel). Scale bar, 50 μm. E, Vascular and pericyte architecture can be visualized in vivo in the mouse brain through a cranial window by multiphoton microscopy using Texas Red‐Dextran, 70 kDa (white) and NeuroTrace 500/525 (fuchsia), respectively. Dextran is not taken up by red blood cells (RBCs) allowing visualization and quantification of RBC flow when imaging speeds are 100 fps or greater