In a recent paper, researchers provided evidence to suggest that the risk factors associated with cardiovascular decline with age interact with amyloid-β in the brain to accelerate cognitive decline. Having more of both produces a worse prognosis, which is not all that surprising. This is the case in many areas of aging and age-related disease: forms of damage and dysfunction interact with one another, making consequences worse than would be the case if they were independent of one another. This is one of the reasons why aging is an accelerating process, starting off slow and picking up pace ever more rapidly as the damage and dysfunction mounts. It is also one of the reasons why it is hard to predict the benefit resulting from any given approach to rejuvenation based on damage repair without actually trying it.
Cardiovascular risk factors such as raised blood pressure and excess fat tissue somewhat measure and somewhat predict the pace at which the complex machinery of blood vessels ages. In particular the failure of smooth muscle in blood vessel walls to correctly react to circumstances with dilation and contraction, the loss of capillaries delivering nutrients to energy-hungry tissues like the brain, and the progression of atherosclerosis, weakening and narrowing blood vessels with fatty plaques. There are other important processes, however, such as the routes for drainage of cerebrospinal fluid, or other ways in which amyloid-β and other metabolic waste might exit the brain.
Past research has shown that there is an equilibrium of sorts between amyloid-β in the brain and amyloid-β in the vascular system outside the brain. It is possible to drain amyloid-β from the brain to some degree by reducing it elsewhere in the body, indicating that there are processes transporting amyloid-β into the blood system, in addition to those removing it via other paths of cerebrospinal fluid drainage. This likely involves the blood-brain barrier, a part of blood vessel walls where they pass through the central nervous system, and thus is impacted by the state of vascular aging and dysfunction. This is the sort of thing one would look into if searching for the mechanisms underlying the relationship noted in the research below.
Alzheimer's disease and cerebrovascular disease are probably the two most common causes of cognitive impairment in the elderly, but even though they often co-occur in individual patients, they are typically viewed as independent contributors. While the presence of amyloid plaques in the brain is considered a hallmark of Alzheimer's disease, some individuals with elevated amyloid levels never develop cognitive impairment. This has led to a search for additional markers beyond brain amyloid to help identify those at increased risk for cognitive decline.
The current study was designed to investigate whether the effects of increased brain amyloid and of vascular risk on cognitive decline are merely additive, reflecting a simple combination of the risks independently contributed by each factor, or synergistic, in which interaction of the two produces an even higher level of risk. The study analyzed data from 223 participants in the Harvard Aging Brain Study, an ongoing study of cognitively normal individuals ages 50 to 90 designed to improve understanding of brain changes affecting memory and cognition that occur with aging.
Upon enrollment in the study, participants receive standard imaging biomarker studies, including PET scans with a compound that reveals amyloid deposits in the brain. Assessment of vascular risk is determined by the Framingham cardiovascular risk score, which is based on factors such as hypertension, body mass index, and histories of diabetes or smoking. Participants also receive standard tests of memory, attention and language, which are repeated at annual follow-up visits.
The results showed that both elevated brain amyloid levels and higher vascular risk, as measured upon study enrollment, were associated with more rapid cognitive decline, with the most rapid changes seen in participants with elevations in both factors. The extent of the interaction between the two measures suggested a synergistic, rather than simply an additive effect.
Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease (AD) is crucial to the success of clinical trials aimed at preventing dementia. The advent of in vivo measures of β-amyloid (Aβ) burden highlighted a preclinical phase of AD allowing for the identification of clinically normal individuals with objective evidence of AD pathology. However, a substantial portion of individuals who are amyloid positive do not show clear evidence of cognitive decline in available longitudinal follow-up data. This is consistent with autopsy data indicating that approximately 30% of clinically normal elderly individuals have signs of elevated Aβ burden on pathological examination. These findings have prompted the search for additional biomarkers that can be used with Aβ burden to identify individuals at maximal risk of cognitive decline.
Multiple studies have demonstrated that cardiovascular risk factors, such as hypertension and hyperlipidemia (which often occur together), are also risk factors for cognitive decline and AD. Consistent with this, recent epidemiological data suggest that declining dementia incidence may be partially because of advances in the treatment of cardiovascular disease. Neuropathological studies indicate that vascular brain changes frequently co-occur with AD pathology in late-onset dementia and that vascular pathology may lower the threshold for cognitive impairment.
The goal of the present study was to examine whether a well-validated, multivariable measure of vascular risk is associated with prospective cognitive decline in a large cohort of clinically normal elderly individuals, either additively or synergistically with Aβ burden.