




































Chang References


Berkeley
Pharma Tech
Journal of Medicine

Correspondence:
yoeu@ucsd.edu

Keywords:
Neurovascular coupling
Dementia
Alzheimer's disease
Parkinson's disease
Vascular dysfunction

Published July 31, 2025

Full Open Access

Creative Commons Attribution
License 4.0

Abstract
Cognitive decline—including dementia, Alzheimer’s disease, and Parkinson’s 
disease—is a growing global health concern. These neurodegenerative disorders 
affect approximately 50 million people worldwide. In the United States, nearly 
two out of three seniors experience some form of cognitive impairment. Since the 
1990s, the prevalence of mild cognitive impairment has been rising in the U.S. 
and is projected to continue increasing for future decades. These alarming trends 
underscore the urgent need for more effective methods of early detection and 
treatment that address the physical, emotional, and cognitive needs of affected 
individuals. Emerging evidence suggests that neurovascular coupling (NVC)—
the critical process linking brain activity to dynamic blood flow—plays an 
essential role in regulating brain energetics and function, and may contribute to 
cognitive dysfunction when impaired. This review delves into the characteristics 
of NVC and the neurovascular unit (NVU), examines early detection strategies 
targeting NVC-related biomarkers, and discusses current and investigational 
treatments for NVC-associated cognitive disorders.

The Pulse of Cognition: Investigating 
Neurovascular Coupling's Role in 
Cognition and Therapeutic Promise for 
Alzheimer’s, Parkinson’s, and Dementia
By: Irene Eu, Cindy Lu, Kalp Soni and Evan Lee



1. Introduction

1.1 Cognitive Decline 

Cognitive decline is an escalating public health concern, driven in part by 
the aging global population. Data show that nearly 20% of adults aged 50 
and older worldwide experience some degree of cognitive decline.¹ In the 
United States, approximately two out of three adults aged 70 or older have 
some form of cognitive impairment, while one in three individuals aged 85 
or older suffers from more severe conditions such as Alzheimer’s disease.2,3 
These statistics highlight the urgent need for comprehensive interventions. 
Effective strategies include pharmacological treatments, nutraceutical 
approaches, and vascular-targeted therapies aimed at addressing both the 
underlying causes and the consequences of cognitive decline. 

Figure 1: DYNASIM Projection of Adults with Cognitive 
Impairments from 2020 to 2060 

Cognitive decline encompasses a range of conditions, including common 
neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s 
disease, and various forms of dementia. AD, for example, involves 
impairments across multiple cognitive domains, affecting memory, 
reasoning, language, coordination, mood, and behavior.4 Similarly, 
Parkinson’s disease presents a range of non-motor and motor symptoms, 
including a diminished sense of smell, digestive issues, and drooling, 

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alongside difficulties in executing normal movements, experiencing tremors, 
and maintaining a stable walking posture.5 Dementia is a broader term that 
refers to the progressive deterioration of memory and other cognitive 
functions, significantly interfering with an individual’s ability to perform 
daily activities. 6 Collectively, these conditions underscore the multifaceted 
nature of cognitive decline and emphasize the need to address these diseases. 

As cognitive decline progresses, impairments in neuronal activity can lead to 
inadequate perfusion of vital brain regions, one of the main causes of 
neuronal damage and cognitive impairments. Therefore, understanding the 
interplay between cognitive decline and neurovascular coupling is crucial for 
developing effective strategies to preserve brain function and slow the 
progression of neurodegenerative diseases. 

1.2 Neurovascular Coupling 

NVC refers to the process by which the metabolic demands of active 
neurons trigger localized changes in cerebrovascular blood flow (CBF). This 
mechanism ensures that the brain receives adequate oxygen and nutrients 
during periods of increased neural activity, thereby maintaining optimal 
perfusion in response to fluctuating neuronal demands.7 

1.2.1 Neurovascular Unit 

The regulation of NVC is coordinated by the neurovascular unit (NVU), a 
complex assembly of neurons, glial cells, and vascular cells. Glial cells—such 
as astrocytes and microglia—play essential roles in supporting and 
protecting neurons. They also contribute to vasculogenesis (the formation 
of new blood vessels from endothelial progenitor cells) and the development 
of synapses.8 Vascular cells, including endothelial cells, help maintain the 
blood-brain barrier (BBB), sense mechanical and hormonal signals to 
regulate CBF. These cells also release substances, like proteoglycans and 
glycoproteins, to adapt blood flow accordingly. Vascular smooth muscle 
cells adjust CBF by modulating vascular tone and capillary diameter in 
response to signals from endothelial cells. Likewise, pericytes influence CBF 
by altering capillary diameter in response to neurotransmitters such as 
noradrenaline and glutamate. This interconnected network ensures the 
delivery of essential nutrients, such asglucose and oxygen, to sustain the 

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energy-demanding brain activity, while also maintaining cerebrovascular 
homeostasis.9

Figure 2: Neurovascular Coupling Mechanism. Stimulation triggers 

glutamate secretion, activating neurons and astrocytes to release nitric oxide (NO), potassium 
(K+), adenosine (Ado), epoxyeicosatrienoic acids (EET), and prostaglandins (PGE2), leading 
to arteriolar vasodilation. Astrocytes also release arachidonic acid (AA), causing 
vasoconstriction, and pericytes are stimulated separately, leading to capillary dilation. 

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Figure 3: The Neurovascular Unit. The neurovascular unit (NVU) consists of 

endothelial cells, pericytes, astrocytes, neurons, and the extracellular matrix. The NVU 
balances the brain microenvironment, regulates cerebral blood flow, facilitates immune cell 
movement, produces growth factors for cell survival, and aids in clearing harmful brain 
byproducts, crucial for brain health. 

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Figure 4: The Blood-Brain Barrier. Vascular stresses affect the blood-brain 

barrier, which regulates brain perfusion. Conditions like hypertension damage the 
endothelium, disrupting the blood-brain barrier, causing microhemorrhages, inflammation, 
and neuronal injury. This process contributes to cognitive decline and dementia. 

1.3 Purpose of Study 

Building upon our review of cognitive decline, we propose that NVC plays 
a critical regulatory role in neurovascular diseases associated with cognitive 
impairment. This study aims to identify early signs of cognitive decline by 
targeting relevant biomarkers and to explore treatment options for 
conditions linked to NVC dysfunction. Specifically, we seek to understand 
how changes in neuronal activity affect blood vessel function and cerebral 
blood flow (CBF) in cognitive disorders such as AD, Parkinson’s disease, 
and dementia. 

2. Histopathological Features of NVC-related Diseases

Histopathological markers of NVC-related diseases, including Alzheimer’s 
and vascular dementia, can be observed through tissue imaging techniques. 
Particularly, the well-known biomarkers of neurofibrillary tangles and 
β-amyloid plaque is associated with Alzheimer’s, while neuronal tissue death 
and myelin breakdown is associated with vascular dementia.10 It is 

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hypothesized that vascular abnormalities contribute to the early progression 
of cognitive disorders and precede the emergence of these histopathological 
features.11 For instance, one study found that patients with vascular 
dementia have significant hippocampal neuronal loss due to microvascular 
pathology.12 These findings support a correlation between vascular 
dysfunction and development of key features of cognitive disorders. 

2.1 Associated Biomarkers 

2.1.1 Pericyte detachment 

Pericytes are instrumental in maintaining the NVU, as they are positioned 
in the unit between endothelial cells, astrocytes, and neurons. They 
contribute not only to the structural maintenance of blood vessels but also 
to the regulation of molecular waste clearance, cell signaling, and cerebral 
blood flow. For example, pericytes influence the activity of proteins that 
preserve the tight junctions of the blood–brain barrier (BBB) and modulate 
the transport of fluid-filled vesicles across it.12 In the cases of higher blood 
pressure, which can stretch the vein and weaken it, pericyte detachment 
from the unit is promoted. Pericyte detachment from around the 
circumference of the vein can lead to BBB permeability, 
neuroinflammation, and issues with neuronal communication, ultimately 
resulting in cognitive dysfunction. Additionally, recent studies have 
implicated pericyte detachment with hypoxia and loss of myelination, which 
leads to the loss of essential connections within the brain.13 

2.1.2 Genetic factors  

The APOEε4 allele, located on chromosome 19, has often been described as 
the greatest genetic risk factor for Alzheimer’s. Although its exact role in 
disease pathology remains incompletely understood, it is known to be 
involved in lipid transport within the brain and the production of 
β-amyloid and tau proteins—key biomarkers of Alzheimer’s disease. 
Emerging research suggests that APOEε4 also disrupts neurovascular 
regulation and exacerbates cognitive decline. Individuals carrying this allele 
exhibit marked pericyte deficiency—approximately 50% fewer pericytes 
compared to individuals without the allele—and increased blood–brain 
barrier breakdown.14 The correlation between APOEε4 with protein 

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aggregate formation and NVC regulation supports our hypothesis that the 
NVC contributes to cognitive decline.15 

2.1.3 Vascular dysfunction 

Given the NVU’s intimate relationship with brain function, vascular 
dysfunction as a whole can act as a root for brain dysfunction. The “2-hit 
vascular hypothesis model”, proposed by Berislav V. Zlokovic, implicates 
vascular dysfunction in exacerbating cognitive decline.16 The “first hit” are 
risk factors such as aging, atherosclerosis, hypertension, diabetes, or stroke, 
all of which jeopardize or breakdown vascular integrity and alter cerebral 
blood flow. The “second hit” refers to the increased Aβ protein levels, 
inflammation, and tau protein levels that result, which causes even further 
decline. This model describes a positive feedback loop between vascular and 
brain dysfunction: injury to the vascular system can accelerate 
neurodegeneration, while neuronal damage can, in turn, worsen vascular 
health.17 Consequently, vascular markers may serve as valuable early 
indicators for the prevention and early-stage intervention of 
neurodegenerative diseases. 

 

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Figure 5: 2-Hit Hypothesis. 2-hit hypothesis model shows that vascular factors and 

genetic factors discussed before serve as predisposing factors to ‘hit 1 vascular damage,’ which 
causes BBB breakdown and ‘hit 2’: physiological manifestations of cognitive decline such as 
protein aggregation and inflammation. These hits cause significant neurodegeneration and 
also (not pictured) a positive feedback loop of brain and vascular damage. 

2.1.4 Blood-brain barrier breakdown 

The blood-brain barrier (BBB) regulates the exchange of compounds 
between the blood and the brain by selectively transporting solutes through 
active transport mechanisms and passive diffusion. 

These include organic compounds such as vitamins, hormones, and 
macromolecules necessary for brain neuron functions. Different levels of 
stress such as hypertension or vascular recanalization can cause the 
breakdown of the barrier. Not only does the breakdown of the barrier result 
in the loss of its functions, but it also allows for the release of 
neurodegenerative compounds such as protein aggregates and pathogens 
that are absorbed by the blood to the brain which leads to neurovascular 
coupling-related diseases. BBB breakdown is also associated with aging, 

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which progressively alters its permeability. Given the BBB’s close functional 
relationship with pericytes, astrocytes, and neurons, its failure is often 
accompanied by dysfunction in these associated cells—providing a broader 
pathological context for detection and diagnosis. 

3. Novel Neuroimaging Techniques 

Recent advances in medical imaging have paved the way for the detection of 
biomarkers and early disease indicators. Neuroimaging plays a critical role in 
diagnosing neurodegenerative diseases, enabling clinicians to detect early 
signs of cognitive impairment, abnormalities in cerebral blood flow, and 
evidence of stroke, while also facilitating ongoing disease monitoring. This 
section explores several state-of-the-art techniques, including in-vivo photon 
imaging, Dynamic Vessel Analyzer (DVA), multimodal imaging platforms, 
fMRI, and fNIRS. 

3.1 In-Vivo Photon Imaging 

In-vivo photon imaging is a powerful technique that allows for deep-tissue 
visualization beyond the superficial layers of the dorsal brain. It has been 
instrumental in identifying correlations between external factors—such as 
dietary salt intake—and internal biomarkers, like elevated tau protein levels, 
a potential indicator of neurodegeneration. Two-Photon Imaging is a 
specific type of In-Vivo Photon Imaging technique. This specific technique 
uses two photons of lower energy to excite a fluorescent molecule. 
Compared to single photon imaging techniques, it allows deeper tissue 
penetration and provides high-resolution images with less photodamage. 
Researchers employ two-photon microscopy to track changes in blood 
vessel diameter, blood flow, and oxygenation levels in response to neuronal 
activity.18 

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Figure 6: Schematic of a 2PF microscope. A two-photon fluorescence microscope 

utilizes a femtosecond laser to send light through xy-scan mirrors, scan and tube lenses, 
focusing on a sample with an objective lens. This induces fluorescence in the sample, which is 
then collected back through the objective lens, filtered by a dichroic mirror, and detected by a 
photomultiplier tube, ultimately translating into an image by a computer.

3.2 Dynamic Vessel Analyzer

In one study, patients with varying degrees of Alzheimer’s disease were 
compared to controls by assessing the retinal blood vessel response to 
flickering lights. Retinal vasculature is a valid proxy for cerebral blood flow 
since they share anatomical and physiological features that stem from a 
shared embryonic origin. To assess these responses, scientists used the 
Dynamic Vessel Analyzer (DVA)—a novel imaging tool that captures 
microvascular dynamics in the eye. As a non-invasive proxy for cerebral 
vasculature, the DVA provides valuable insights into neurovascular 
function. Results revealed that patients with moderate or mild dementia 
from Alzheimer’s had emphasized arterial and venous dilation, as well as 
delayed arterial reaction to the flickering lights. These findings suggest that 
increased and delayed retinal neurovascular coupling, perhaps caused by 
damaged feedback loops or excessive activity of retinal neurons, is associated 
with Alzheimer’s. As a non-invasive and accessible diagnostic tool, the DVA 

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holds promise for monitoring retinal and vascular changes linked to 
Alzheimer’s disease and may aid in tracking disease progression.19 

Figure 7: Static analysis performed by the Dynamic Vessel Analyzer. 
The technology gives valuable glimpses into arterioles (red segments) and venules (blue 
segments) 

3.3 Multimodality Imaging Platforms 

Traditional high-resolution microscopy offers excellent detail but is limited 
by its small field of view. To overcome this limitation, researchers in one 
study employed a multimodality imaging approach to investigate the role of 
calcium ion (Ca²⁺) fluctuations in astrocytes, key glial cells involved in 
maintaining the NVU. Using electrical stimulation in mice, researchers 
observed that astrocytes exhibited a delayed response to stimulation, while 
cerebral blood flow increased rapidly. This finding suggests that astrocytes 
contribute to the coupling between neuronal activity and blood flow. 
Additionally, the stimulation induced vasoconstriction—the narrowing of 
blood vessels—indicating that astrocytes may regulate blood flow not only 
during periods of high neural activity but also at rest. By integrating 
multiple imaging modalities, the study provided a more comprehensive 

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understanding of astrocytic function in cerebral perfusion and cognitive 
maintenance.20 

3.4 fMRI (Functional Magnetic Resonance Imaging) 

fMRI is a widely used, non-invasive technique for visualizing brain activity 
by measuring changes in blood oxygenation levels. It relies on BOLD 
(blood-oxygen-level-dependent) contrast, which detects variations in the 
magnetic properties of oxygenated and deoxygenated hemoglobin. fMRI is 
repeatable, widely available, and offers superior spatial resolution compared 
to other neuroimaging methods. It enables in-depth, whole-brain analysis of 
functional activity. However, fMRI has limitations: it is contraindicated for 
individuals with metal implants or devices from prior medical procedures, 
and its sensitivity to movement makes it less suitable for use during physical 
activity or with populations such as infants. 

3.5 fNIRS (Functional Near-Infrared Spectroscopy) 

Although fMRI is considered one of the most advanced neuroimaging 
modalities, functional near-infrared spectroscopy (fNIRS) has emerged as a 
promising alternative or complementary technique. Like fMRI, fNIRS is 
non-invasive and measures hemodynamic responses in the brain, but it does 
so using near-infrared light instead of magnetic fields. fNIRS is relatively 
inexpensive, portable, and tolerant to motion, making it suitable for 
dynamic settings and use in young or mobile populations. However, it has 
limitations in terms of probe placement and depth of measurement, 
typically capturing data only from the frontal cortex and superficial cortical 
areas. 

 

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Figure 8: Functional near-infrared spectroscopy. Functional near-infrared 
spectroscopy (fNIRS) is used for non-invasive monitoring of changes in oxy- and deoxy-
hemoglobin levels within the brain. It involves a configuration of fiber optic-based light sources 
and detectors arranged on a flexible head cap worn by the participant. 

4. Neurovascular Coupling Targeted Market
Therapeutics

Exploring new treatments for brain health is essential in addressing 
cognitive decline. This article introduces several options, including Cocoa 
Flavonoids (CF), Nicotinamide Mononucleotide(NMN), i-NO Pericyte 
Relaxant, Inorganic nitrate supplementation, and Nicotinamide Adenine 
Dinucleotide (NAD) supplementation. Each offers potential benefits, but 
future research is required to confirm their safety and effectiveness. 

4.1 Cocoa Flavonoids (CF) 

Cocoa flavonoids (CF) are recognized for their neuroprotective attributes, 
antioxidant and vasodilatory properties, and their ability to inhibit 
cholinesterase and tau formation. Despite these promising attributes, their 
effects appear limited in scope. Current evidence suggests that CF primarily 
increases BOLD (blood-oxygen-level-dependent) responses in specific brain 
regions—namely the supramarginal gyrus of the parietal lobe and the 
inferior frontal gyrus.21 The effects of CF intake are not well understood, 
and clinical studies are required to further investigate their impact. 

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4.2 Nicotinamide Mononucleotide (NMN) 

Nicotinamide Mononucleotide (NMN) is another treatment option that 
enhances endothelial NO-mediated vasodilation and serves as an NAD+ 
intermediate. It is also recognized for improving spatial working memory 
and movement coordination. However, most research has focused on its 
vascular effects in large arteries, such as the aorta, leaving its broader 
systemic and neurological interactions underexplored. Moreover, some 
clinical trials have reported adverse effects, raising concerns about the safety 
and long-term efficacy of NAD⁺ intermediates like NMN. These findings 
underscore the need for further investigation to better understand its 
therapeutic viability.22 

4.3 i-NO Pericyte Relaxant 

i-NO Pericyte Relaxant demonstrates potential as treatment by opening 
constricted blood vessels, becoming neuroprotective in other mammals, and 
assisting in recanalization and pretreatment. 

While showing strength as a neuroprotective agent and in aiding blood flow, 
this presents certain challenges. For example, its efficacy can be 
compromised by interactions with other chemicals such as adenosine 
triphosphate, norepinephrine, angiotensin II, and intracellular reactive 
oxygen species. These chemicals can potentially reduce its therapeutic 
benefits. Additionally, there are reported side effects that could be 
detrimental to patients. Given these issues, it is clear that extensive  human 
clinical trials are required to verify the treatment's safety and to ensure its 
therapeutic efficacy is consistent and reliable. 

4.4 Inorganic nitrate supplementation 

Inorganic nitrate supplementation is a non-pharmaceutical approach used 
to support cerebral vascular health. It is available over the counter in 
supplement form and naturally occurs in dietary sources such as beetroot 
juice. Inorganic nitrates are known to reduce blood pressure, enhance 
endothelial function, and potentially improve athletic performance. 

While generally well-tolerated and being a non-pharmaceutical option, some 
individuals may experience side effects such as stomach discomfort, changes 

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in bowel movements, or colored urine. A notable concern is the potential 
for drug interactions, particularly with medications that affect nitric oxide 
pathways, which may increase the risk of conditions like 
methemoglobinemia. Despite its benefits, the long-term effects of inorganic 
nitrate supplementation remain unclear. Further research is necessary to 
fully understand its efficacy and safety for prolonged use. 

4.5 Nicotinamide Adenine Dinucleotide (NAD) supplementation 

Nicotinamide adenine dinucleotide (NAD) supplementation has emerged 
as a promising strategy to mitigate age-related cognitive decline. NAD is a 
coenzyme essential for cellular metabolism and energy production, but its 
levels naturally decline with age, which may contribute to reduced brain 
function and vascular integrity. Supplementation typically involves the use 
of NAD precursors, such as nicotinamide riboside (NR) and nicotinamide 
mononucleotide (NMN), which are intended to boost intracellular NAD⁺ 
levels. This, in turn, may enhance mitochondrial function and promote 
neurovascular health. However, side effects such as nausea, fatigue, 
headaches, and diarrhea have been reported. Although these supplements 
are generally considered safe at recommended doses, the long-term effects 
remain uncertain. Further clinical trials are needed to evaluate the full 
therapeutic potential and safety profile of NAD supplementation for 
cognitive health. 

Currently, researchers are conducting two ongoing significant clinical trials, 
NCT03617302 and NCT05483465, related to the Neurovascular 
Coupling in cognitive decline. These studies aim to understand how 
changes in the interaction between neuronal activity and cerebral blood 
flow contribute to cognitive impairments associated with aging. By 
investigating different interventions, these studies aim to identify 
interventions that may slow or mitigate cognitive decline in older adults. 

4.6 Inorganic Nitrate Supplementation on Cerebrovascular Aging 
and Arterial Stiffness 

The first ongoing clinical study "Inorganic Nitrate Supplementation on 
Cerebrovascular Aging and Arterial Stiffness" focuses on examining the 
effects of inorganic nitrate supplementation, particularly from beetroot 

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juice, on aging cerebrovascular systems and arterial stiffness.23 Launched on 
November 1, 2018, the study is expected to conclude on June 30, 2024. 
This randomized, double-blind, crossover study enrolled 53 
community-dwelling older adults, randomly assigned to either an 
experimental or control group. The experimental group received nitrate-rich 
beetroot juice, while the control group consumed nitrate-depleted beetroot 
juice. The primary outcomes measured were the acute changes in carotid 
artery stiffness, assessed through ultrasonography and applanation 
tonometry, and changes in cerebral blood flow which were measured using 
4D pc VIPR MRI technology. The 4D pc VIPR MRI is an advanced 
imaging technique that generates detailed, dynamic images of blood flow in 
cerebral arteries, allowing researchers to visualize circulation patterns 
throughout the brain. Carotid artery stiffness is a critical biomarker of 
cerebrovascular aging, as reduced compliance in these vessels can impair 
cerebral perfusion. This study underscores the potential role of dietary 
nitrate supplementation in supporting vascular function and mitigating 
cognitive decline associated with aging. 

4.7 The Effect of NAD Supplementation on Brain Vascular Health 
in Aging 

The second study "The Effect of NAD Supplementation on Brain Vascular 
Health in Aging," delves into its effects on brain vascular health in aging 
individuals.24 The objective is to ascertain whether Nicotinamide Riboside, 
a precursor to NAD, can enhance brain health and memory in older adults 
by replenishing NAD levels. The trial began on May 3, 2023 and is 
scheduled for completion in December 2027. This randomized, 
double-blind, placebo-controlled parallel study involves 214 
community-dwelling older adults with normal cognitive function. 
Participants in the experimental group receive oral nicotinamide riboside (1 
gram per day) for 8 weeks, while the control group receives an 
indistinguishable placebo. Primary outcomes include changes in 
neurovascular coupling, assessed using functional near-infrared 
spectroscopy, and alterations in neuronal activity, measured through EEG. 
EEG provides spectral data through power spectral density analysis, 
enabling researchers to assess brain activity before and after treatment, 
reported as a percentage change from baseline. This study is particularly 

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significant as it explores the direct impact of NAD⁺ replenishment on brain 
vascular health, with the potential to prevent or delay cognitive decline in 
the aging population. 

5. Future Directions  

Future directions of research on NVC-associated cognitive decline could 
include conducting longitudinal studies spanning 5-10 years to track the 
efficacy of interventions targeting NVC in individuals with cognitive 
impairments. This could also include the development of combination 
therapies, such as medicinal treatments and lifestyle interventions to 
investigate the benefits of improving overall well-being on brain health. In 
addition, genetic factors play a critical role in cognitive decline and warrant 
deeper investigation. While the APOEε4 allele is a well-known genetic risk 
factor, emerging evidence suggests that other genes—such as CLDN5, 
which is associated with blood–brain barrier integrity—may also be 
implicated in NVC dysfunction.21 Future research could explore epigenetic 
approaches, including gene expression modulation, as a potential 
therapeutic strategy for NVC-related diseases. 

6. Conclusion 

As discussed, the growing prevalence of cognitive decline, including 
Alzheimer’s, Parkinson’s, and dementia, presents a significant challenge to 
public health systems worldwide. This review highlights the important role 
of NVC in regulating cerebral blood flow and brain health, both of which 
are essential in mitigating cognitive decline and managing 
neurodegenerative diseases. 

Innovations in biomarkers–pericyte detachment, APOEε4 gene expression, 
vascular dysfunction in accordance with the 2-hit hypothesis model, and 
BBB breakdown–and advanced neuroimaging techniques–in-vivo photon 
imaging, Dynamic Vessel Analyzer, multimodality imaging platforms, 
fMRI, fNIRS–can be the key for the early detection and combating of 
NVC-related diseases. Additionally, NVC-targeting market therapeutics 
provide a look into future treatment. Substances like cocoa flavonoids and 
inorganic nitrate supplementation are being explored for their potential 
benefits in improving brain vascular health and cognitive function. With 

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continued research, these market therapies could be developed into effective 
treatments for both early and late stages of NVC-related symptoms. 
Ongoing research is necessary to refine these therapies to ensure both 
effectiveness and safety across various stages of disease progression. 
Although many of these interventions are still in early-stage research and 
suffer from limited funding and clinical validation, they show promise for 
future therapeutic development. In summary, the integration of advanced 
neuroimaging techniques with targeted biomarker detection holds 
considerable promise for improving the early diagnosis, monitoring, and 
treatment of cognitive decline. Focusing on the neurovascular unit as a 
therapeutic target may pave the way for more effective and personalized 
interventions in the fight against neurodegenerative diseases. 

 

 

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