At rest, without any breath-holding, injections, or notable exertion, your brain performs a remarkable feat. Its blood vessels are in a state of constant micro-adjustment — expanding and contracting in response to minor changes in blood pressure and carbon dioxide — ensuring that the approximately 100 billion neurons within receive a consistent supply of oxygen. This process is so automatic that we remain oblivious to it. However, Amaryllis Tsiknia, a PhD candidate at the neuroimaging institute of the University of Southern California, believes that when this system begins to struggle, the early warning signs might emerge years before any memory issues surface.
Her research team has recently uncovered evidence to support that theory. In a study published this month in Alzheimer’s & Dementia, Tsiknia and her colleagues demonstrated that slight variations in the efficiency with which the brain manages its own blood flow and oxygen delivery are closely linked to two defining characteristics of Alzheimer’s disease: the accumulation of amyloid plaques and the reduction in size of the hippocampus, the seahorse-shaped structure deep within the temporal lobe that plays a critical role in the formation of new memories.
The measurements did not involve MRI machines, radioactive tracers, or demanding procedures. Participants simply remained still for eight minutes while the team observed them using two non-invasive methods. Transcranial Doppler ultrasound monitored blood flow velocity in a primary brain artery by sending sound waves through the skull; near-infrared spectroscopy, functioning similarly to a pulse oximeter but placed over the forehead, assessed the amount of oxygen reaching the cortex. These continuous signals allowed an advanced mathematical model to extract five distinct indices — each one reflecting a slightly different aspect of how the blood vessels respond to spontaneous changes in pressure and CO2 levels.
Higher scores on those indices indicated that the brain’s vessels behaved more like those found in cognitively healthy individuals. Lower scores suggested abnormalities.
“Amyloid and tau are frequently regarded as the main contributors to Alzheimer’s disease, but blood flow and oxygen delivery are also essential,” states Tsiknia. “Our findings indicate that when the brain’s vascular system operates in a manner more akin to healthy aging, we also observe brain features associated with improved cognitive health.” Participants whose vascular indices fell within the healthier range generally had less amyloid accumulation throughout their cortex and, separately, larger hippocampal volumes — both well-recognized indicators of reduced Alzheimer’s risk, routinely measured by PET and MRI scans that can cost thousands of pounds per session.
What’s particularly fascinating is that the associations persisted even after the researchers considered age, sex, APOE ε4 status (the primary genetic risk factor for the most common form of the disease), and cognitive test scores. The vascular signal was indicating something independent. Senior author Meredith Braskie, an assistant professor of neurology at the Keck School of Medicine, describes it succinctly: “These vascular measures reveal something significant about brain health. They seem to correlate with what we observe through MRI and PET scans typically utilized to investigate Alzheimer’s disease, offering crucial insights into how vascular health and standard measures of Alzheimer’s disease risk may be interconnected.”
These findings contribute to an expanding body of research — referred to as the vascular hypothesis of Alzheimer’s — proposing that the disease is not solely a narrative of malfunctioning amyloid and tau proteins. Vascular risk factors such as hypertension correlate with an increased risk of dementia; managing high blood pressure seems to mitigate that risk. The suggested mechanisms converge on a shared issue: when the supply of blood to the brain diminishes chronically, neurons receive less oxygen, the integrity of the blood-brain barrier declines, and conditions that promote amyloid accumulation emerge. Animal studies have further elaborated on this relationship, indicating that amyloid plaques themselves hinder vascular regulation, which in turn accelerates additional plaque buildup. A vicious cycle, in essence.
The hippocampus could be particularly vulnerable to these effects, which might explain why memory tends to be the first cognitive function to decline. The microvascular structure that serves the hippocampal tissue differs from that in the neocortex — its capillaries are less dense, and neurovascular coupling is weaker — rendering it more susceptible to even minor reductions in perfusion.
However, the study also provides a practical perspective. Arthur Toga, director of the Stevens Neuroimaging and Informatics Institute and a co-author of the paper, highlights that “comprehending how blood flow and oxygen regulation interact with amyloid and brain structure unveils new avenues for early detection and possibly prevention.” The tools necessary for this study — a handheld ultrasound device and a spectroscopy headset — are portable, relatively inexpensive, and do not require patients to hold their breath on cue or endure the claustrophobic experience of an MRI machine. This is particularly significant for large-scale screening or for older individuals who may not cope well with more invasive procedures.
Naturally, there are limitations. The study was cross-sectional, which means it captured a specific moment in time rather than following individuals over an extended period. Thus, it cannot definitively resolve the chicken-and-egg dilemma: does poor vascular regulation lead to the