**3.2 Cerebral vascular aging**

Healthy functional cerebral vessels can coordinate with CBF and appropriately supply blood to the brain [65]. As aging progresses, however, cerebrovascular function declines, which can increase the possibility of ischemic stroke, intracerebral hemorrhages (ICHs), microbleeds, and cognitive decline [64]. Cerebrovascular aging has the following features, which can lead to age-related cerebrovascular diseases:


**9**

dementia are complex [90, 98].

duction, and oxidative stress [103].

*Aging, Cerebrovascular Burden, and Cognitive Decline DOI: http://dx.doi.org/10.5772/intechopen.89854*

after vascular damage to develop newer therapeutic approaches.

**4. Aging and vessel-related cognitive decline**

VaD, will increase by 45% in 2050 compared to 2015 [92].

With respect to neural activity, cerebrovascular reactivity (CVR) can be used to measure the response levels of brain blood vessels to various stimuli. Very recent evidence has shown that cerebral vessel contractility and dilation decrease as aging progresses and have effects on the neurovascular damage mediated by NO [86]. In addition, there is an induction of vasoconstrictive factors in the cerebral endothelium [87]. Since the vessel wall undergoes structural changes through the normal aging process, it is a natural and frequently found phenomenon that the basement membrane becomes thicker but smooth muscle cells and elastin layer are thinner [88]. These different responses between young and old adults have been demonstrated using bloodoxygen-level-dependent functional MRI (BOLD fMRI) data [89]. As a result of these collective findings, it is now considered that the vasculature plays a critical secondary cause in many neurodegenerative diseases, particularly in neurovascular dysfunction. Therefore, there needs to be an increase in recognition and a focus on cognitive decline

Dementia is an irreversible cognitive condition. According to a statistical report,

Mild cognitive impairment (MCI) is included as a cognitive-related disease in the older population. Although MCI is also considered as a pre-step proceeding to dementia, patients with MCI still fortunately have a chance of recovery or at least have a chance to delay the progression of the disease. Therefore, new strategies are urgently needed to diagnose and treat patients with MCI. Some blood factors such as MCP-1 or IL-6 have been suggested to be biomarkers for estimating the progression in cognitive decline because the vascular blood factors are modified in patients with MCI [93]. Some clinical studies have shown that VCID occurs in 25–30% of aged people who have had a previous stroke [94, 95]. Stroke is known to be the second leading cause of cognitive dysfunction. Furthermore, a clinical history of stroke increases the risk of cognitive dysfunction up to fivefold [96, 97]. Therefore, the symptoms of poststroke dementia could be related to the occlusion site, occlusion type, occlusion numbers, and lesion volume in the brain. There are studies that have shown that poststroke cognitive decline is related to the pathology of cerebrovascular disease and dementia, although the mechanisms involved in poststroke

Aging is complex and vulnerable to cognitive decline as well as brain disorders

[99]. A recent study concluded that cognitive impairment in aged adults with depression is correlated with the SASP profile [100]. This study showed that the levels of the SASP were highest in participants with both late-life depression (LLD) and MCI (**Figure 1**). This study suggests that cognitive impairment in LLD is linked to an aging-specific molecular profile, which might be an indicator for aging people with LLD who develop dementia [100]. Recent clinical studies have reported that depression and cognitive impairment in aging are associated with the regulation of the SASP: immune-inflammatory response [101], proteostasis [102], signal trans-

7.7 million people are newly diagnosed with dementia every year [90]. Among these, patients with vascular cognitive impairment and dementia (VCID) compose over 20% of the total dementia patient population [91]. By 2030, the number of older people (>60 years of age) is predicted to increase by 56% compared to the number in 2015, and it will continue to grow year by year. Finally, by 2050, our society will become a superaged society, and it is evident that the prevalence of neurodegenerative diseases will increase. Cognitive-related diseases, such as AD or *Aging, Cerebrovascular Burden, and Cognitive Decline DOI: http://dx.doi.org/10.5772/intechopen.89854*

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

subject to hypoperfusion [71].

**3.2 Cerebral vascular aging**

described above.

[79, 80].

leukoencephalopathy [81–83].

molecules [85].

diseases:

among healthy humans in the plateau region [71]. The report also suggested that hypertension and a higher pulsatile rate might disrupt cerebral autoregulation, which make subjects prone to neurodegenerative diseases because the aging brain is

Healthy functional cerebral vessels can coordinate with CBF and appropriately supply blood to the brain [65]. As aging progresses, however, cerebrovascular function declines, which can increase the possibility of ischemic stroke, intracerebral hemorrhages (ICHs), microbleeds, and cognitive decline [64]. Cerebrovascular aging has the following features, which can lead to age-related cerebrovascular

i.Endothelial senescence: many studies have shown the presence of senescent endothelial cells in aged cerebrovascular lesions, which is triggered by the accumulation of ROS [31] and modulated by inflammatory factors, as

ii.Oxidative stress and inflammation: in vessels' walls, ROS increase nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity associated with aging [7, 72, 73]. These findings have been reported in both nonclinical and clinical studies. It is also well known that the vasculature can be easily

damaged by vasculopathy, including atherosclerosis [74–76].

iii.Microvascular rarefaction: this is a condition where the microvascular

network and its density are reduced. Rarefaction has been detected in some brain subregions, particularly in the hippocampus. Since the hippocampus is involved in memory, it could lead to memory loss [77, 78]. Circulating endothelial progenitor cells have been shown to be diminished by aging, which is linked to white matter changes and a decline in cognitive function

iv.Arterial stiffness: this is a major characteristic of vascular aging. Vascular stiffness increases blood flow velocity and blood pressure. Arterial stiffness results in an increase in systolic pressure and a decrease in diastolic pressure.

v.Vascular lumen narrowness: the accumulation of toxic molecules in the vessel walls makes the vascular lumen narrow. There have been clinical studies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) that have examined Notch3 molecules in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The high-temperature requirement A serine peptidase 1 (HTRA1) is also explored in cerebral autosomal recessive arteriopathy and

vi.CBF reduction: generally, hypoperfusion in the cerebral circulation is suggested to lead to cognitive impairment [84]. In cases of mild hypoperfusion, synaptic plasticity is impaired by a reduction in protein synthesis during learning and memory consolidation [2]. Under severe hypoperfusion, there is failure in the formation of the action potential, disruption in the acid–base balance, occurrence of neuronal edema, and accumulation of neurotic

**8**

With respect to neural activity, cerebrovascular reactivity (CVR) can be used to measure the response levels of brain blood vessels to various stimuli. Very recent evidence has shown that cerebral vessel contractility and dilation decrease as aging progresses and have effects on the neurovascular damage mediated by NO [86]. In addition, there is an induction of vasoconstrictive factors in the cerebral endothelium [87]. Since the vessel wall undergoes structural changes through the normal aging process, it is a natural and frequently found phenomenon that the basement membrane becomes thicker but smooth muscle cells and elastin layer are thinner [88]. These different responses between young and old adults have been demonstrated using bloodoxygen-level-dependent functional MRI (BOLD fMRI) data [89]. As a result of these collective findings, it is now considered that the vasculature plays a critical secondary cause in many neurodegenerative diseases, particularly in neurovascular dysfunction. Therefore, there needs to be an increase in recognition and a focus on cognitive decline after vascular damage to develop newer therapeutic approaches.
