Age‐related changes in cerebrovascular health and their effects on neural function and cognition: A comprehensive review

Figures

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  FIGURE 1. Cerebrovascular damage progresses from loss of elasticity in the larger arteries to distal downstream damage to the microvasculature. Impaired cerebrovascular function leads to reduced efficiency in neural processing through damaged myelination and impaired neurovascular coupling mechanisms. Eventually, cerebrovascular dysfunction leads to ischemia, causing cellular impairment or cell death. Together, these effects manifest as reductions in cognitive function

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  FIGURE 2. Watershed regions in the brain exist in areas between the ends of major feeding arterial systems. Classically, these regions are described in two categories. Regions on the cortex between the major arterial systems feeding the cortex (purple), or internal regions in the periventricular white matter (red) between the superficial and deep branches of the middle cerebral artery or the middle cerebral and anterior cerebral arteries. The cortical watershed regions (purple) usually encompass a thin fronto‐parasagittal wedge from the anterior horn of the lateral ventricle to the frontal cortex, a parieto‐temporo‐occipital wedge from the occipital horn of the lateral ventricle to the parieto‐occipital cortex, or a strip on the superior cortex. The internal watershed areas are usually found in white matter, corona radiata, or the centrum semiovale

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  FIGURE 3. Arterial stiffness can be measured using diffuse optical tomography, which is sensitive to different properties of the pulse flow wave propagating through local arteries (pulse‐DOT). These properties include amplitude of the flow wave, reflecting local pulse pressure, transit time, reflecting upstream arterial compliance, and shape, which is a complex combination of both downstream and upstream vascular properties and reflects flow pulsatility. These properties change with age and correlate to other measures of brain health and cognition

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  FIGURE 4. This simplified view shows how some of the signaling mechanisms involved in neurovascular coupling are disrupted in aging. Increases in NO resulting from mitochondrial dysfunction and inflammatory signaling at the neurovascular junction promote vasodilation. In contrast, inflammatory signaling in endothelial cells promote potent vasoconstriction. Overall, inflammatory signaling, from mitochondrial dysfunction or from exposure to external toxins coming through an impaired BBB, may lead to impairments in the coordinated neurovascular coupling mechanisms that dilate local vasculature in response to neural activity

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  FIGURE 5. A framework for viewing the effects of cerebrovascular impairment on cognition as a hierarchical cascade of effects. Gray arrows represent the hypothesized cascade. Orange arrows represent pairwise relationships between the levels. The signs next to the arrows represent the direction of the pairwise relationships. WMSAs, white matter signal abnormalities. From Kong et al. (2020), reprinted with permission

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  FIGURE 6. Commonly used methods in cognitive neuroscience and psychophysiological research primarily measure different components of neurovascular coupling. In neurovascular coupling, cellular metabolism at the neurovascular unit signals local vasodilation. This increases blood flow to active areas, which interacts with metabolism to alter the nearby blood oxygenation. ASL, arterial spin labeling; BOLD fMRI, blood‐oxygen‐level‐dependent functional magnetic resonance imaging; CMRO2, cerebral metabolic rate of oxygen; DSC, dynamic susceptibility contrast perfusion imaging; EEG, electroencephalogram; ERPs, event‐related potentials; EROS, event‐related optical signal; fNIRS, functional near‐infrared spectroscopy; MEG, magnetoencephalography; 15O‐PET, oxygen‐15 positron emission tomography; Pulse‐DOT, brain arterial pulse wave measured with diffuse optical tomography; VASO, vascular‐space‐occupancy magnetic resonance imaging

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  FIGURE 7. Changes in both neurovascular energetics and neurovascular coupling could mediate differences in the BOLD signal in aging. In younger adults, neural activity leads to an increase in oxygen extraction, which increases the ratio of deoxy/oxy‐hemoglobin. However, this change is offset by a much larger increase in CBF from local vasodilation. Overall, there is a robust BOLD signal coupled to the neural activity. In older adults, both neurovascular energetics and neurovascular coupling mechanisms may change. In this example, the same task‐related neural activity may lead to greater oxygen usage in older adults, due to lower metabolic efficiency. The increase in deoxy‐hemoglobin in older adults compared to younger adults may lower the BOLD signal. In addition, impaired neurovascular coupling may reduce vasodilation, leading to smaller decreases in the ratio of deoxy/oxy‐hemoglobin. Together, these lead to a reduced signal‐to‐noise in the BOLD signal of older adults