Cardiovascular Aging Contributes to Brain Aging

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The brain is an energy-hungry organ, and is sensitive to reductions in the blood supply of oxygen and nutrients. Cardiovascular aging can reduce that supply, whether through conditions such as heart failure, or the progressive loss of density in capillary networks that occurs throughout the body with advancing age, or an accelerated pace of rupture of tiny vessels in the brain, or disruption of the blood-brain barrier, allowing unwanted molecules and cells to enter the brain. Thus, as researchers here note, we would expect to see correlations between cardiovascular disease, or risk factors for cardiovascular disease, and damage and dysfunction in the brain.


Age-related changes in the cerebrovascular system include structural reorganization of the vascular beds, reduced vessel elasticity, and disintegration of the blood-brain barrier. Further observations include reduced cerebral perfusion, and increased lesion burden in the cerebral white matter. Lesions can be observed as white-matter hyperintensities (WMHs) upon magnetic resonance imaging (MRI). They arise from ischemia, hypoperfusion, blood-brain-barrier breakage, and inflammation and are considered manifestations of cerebral small-vessel disease. WMHs are highly prevalent in aging and predictive of broad-ranged cognitive decline, dementia, and mortality.

Dopamine (DA) has been identified as an important modulator of cognitive functions. Maladaptive DA signaling typically gives rise to cognitive impairment, whereas increased DA transmission, if not excessive, may improve performance. Numerous positron emission tomography (PET) studies have demonstrated reduced availability of DA constituents in older individuals, with links to reduced cognitive performance. The age sensitivity of the DA system has therefore been suggested to modulate cognitive trajectories in aging. Research suggests relationships among vascular function, DA status, and atrophy in pathological and normal aging. Cognitive impairments in Parkinson’s disease (PD) have been related to deficits in perfusion and DA decline, which are exacerbated in presence of WMHs. Increased WMH burden in normal aging is paralleled by decreased grey-matter and white-matter volume, and has been associated with reduced DA transporter and D1 receptor availability.

Thus we evaluated the interrelation among WMH burden, cerebral perfusion, DA D2-receptor (D2DR) availability, grey- and white-matter structure, and cognition in 181 healthy, older adults aged 64-68 years. Higher cardiovascular risk as assessed by treatment for hypertension, systolic blood pressure, overweight, and smoking was associated with lower frontal cortical perfusion, lower putaminal D2DR availability, smaller grey-matter volumes, a larger number of white-matter lesions, and lower episodic memory performance. Taken together, these findings suggest that reduced cardiovascular health is associated with poorer status for brain variables that are central to age-sensitive cognitive functions, with emphasis on DA integrity.

Link: https://doi.org/10.1002/acn3.50927

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