Raphael ThysThe aging of the cardiovascular system contributes to the aging of the brain. As the authors of today's open access review paper note, the relationship isn't straightforward and is mediated by a range of mechanisms that are far less direct than the pressure damage caused by hypertension, or the consequences of a reduced blood supply to the brain. One thing to consider about this relationship is that some fraction of cardiovascular disease in the wealthier regions of the world appears to be self-inflicted. Hunter-gatherers such as the Tismane exhibit little cardiovascular disease. To the degree that the brain declines because the vasculature declines, these populations are likely to also exhibit a lower incidence of dementia.
To restate in a more applicable way, maintaining the level of trim physical fitness needed to run an antelope to exhaustion every so often, and keeping that up into later life, is both possible and beneficial. Those of us seduced into an unhealthy lifestyle of excess fat and little exercise by the modern reality of cheap calories and readily available engines of transport are paying the price, slowly over time, and have charted a course for a worse old age with a greater level of cognitive decline.
Cardiovascular Disease and Alzheimer's Disease: The Heart-Brain Axis
A plethora of shared pathophysiological processes link the cardiovascular and the cerebrovascular system forming the heart-brain axis. Abnormalities in the heart-brain axis are likely associated with the incidence of cardiovascular disease (CVD) and Alzheimer's disease (AD), two of the leading aging-related chronic diseases. The precise mechanisms and molecular processes that modulate the heart-brain axis remain elusive. However, there are several common CVD risk factors that are increasingly linked with AD dementia and AD-related dementia incidence. The links between CVD and AD have been confirmed in observational cohorts as well as experimental data. Although the pathophysiologic mechanisms for AD have not been fully elucidated, studies link AD with CVD manifested by hypertension and intracranial and extracranial atherosclerosis and arteriosclerosis. Both AD and CVD are progressive diseases with decades-long incubation periods before clinical manifestation. Although aging is the greatest risk factor, AD and CVD also share several modifiable risk factors, such as smoking, lack of physical exercise, hyperlipidemia, and hypertension. Furthermore, recent studies have suggested that subclinical CVD in midlife may be associated with incidence of dementia, including AD dementia, in late life. Atherosclerosis is the deposition of fibrofatty lesions in the arterial walls, and arteriosclerosis is the stiffening of the media of the arterial wall as a result of degeneration of connective tissue, particularly elastin. Although both atherosclerosis and arteriosclerosis commonly occur together, they are thought to have differing causes and classical risk factors. The pathogenesis of atherosclerosis is centralized to the collection of lipoproteins (mainly low-density lipoprotein particles in the subendothelial intima). The smaller and cholesterol enriched lipoprotein particles easily cross the arterial wall and undergo modification via oxidation, acetylation, and aggregation. These modifications allow an easier capture by macrophages and smooth muscle cells, which then form foam cells inducing an inflammatory cascade response. How exactly does atherosclerosis or arteriosclerosis lead to AD or AD-related dementias independently of ischemic brain lesions or neurodegenerative pathology? Atherosclerosis could contribute to brain dysfunction and axonal damage by a subtle reduction in microvascular perfusion without causing overt ischemic lesions. Blood-flow-independent aspects of neurovascular function, such as blood-brain barrier permeability, neurotrophic support by endothelial cells or neuroimmune modulation, could also be involved. Clinical events in arteriosclerosis are postulated to be secondary to the systolic hypertension that results from aortic stiffening as well as other adverse hemodynamic effects. Arteriosclerosis, marked by measures of pulse wave velocity (among others), is associated with cognitive impairment. The brain, which is both a high flow and low impedance organ, is susceptible to damage from increased pulse pressures. Increased pulse pressure is also associated with cerebrospinal fluid amyloid-β (Aβ) and tau levels. Hypertension, a primary factor in arteriosclerosis formation, is associated with in vivo measures of Aβ deposition and Aβ interacts with vascular risk factors to increase cortical thinning.