Time After Time: Environmental Influences on the Aging Brain

Elizabeth Grossman


Environ Health Perspect. 2014;122(9):A238-A243. 

In This Article

Neurotoxic Agents

In the past 10 years, however, a number of studies[5–10] have looked at the effects of chronic low-level lead exposure on adult humans' cognitive abilities. The findings of such studies suggest that lead that has accumulated in bones can be mobilized over time as part of the aging process, resulting in exposures that adversely affect adults' cognitive skills later in life.

One study assessed 466 elderly participants in the VA Normative Aging Study who were environmentally but not occupationally exposed to lead. The study showed that higher bone lead levels were associated with steeper declines in these men's cognitive skills over several years of followup, even after adjusting for confounding factors.[11] Other work assessed the impacts of low-level lead exposure combined with self-reported chronic stress in 811 older men participating in the same study. It, too, found these exposures to be associated with impaired cognitive ability.[12]

Other metals may adversely affect neurological function in later life by either acting directly on the brain or adversely impacting other organs or hormones that maintain healthy neurological function. For example, cadmium can cause kidney disease,[13] which is associated with cognitive problems.[14,15] Like lead, cadmium is stored in the body, primarily in the kidneys and liver but also in joints and other tissues, where it has a biological half-time of decades.[16] Rodent studies indicate cadmium can also interact with the estrogen receptor and interfere with how the body uses calcium and zinc,[17] both of which play a role in nervous system function.

Similarly, lead and mercury have been associated with liver disease,[18] which itself is associated with adverse neurological health effects, including a condition that produces a type of neuronal plaque associated with Alzheimer's disease.[19] Chemical exposures that adversely affect kidney and liver function can also hamper the body's ability to detoxify and excrete environmental toxicants, thus letting them remain in the body—an effect that may be particularly problematic in advanced age when a body's defense mechanisms are in decline.[20]

It was long assumed that the brains we were born with were the brains we died with—minus whatever brain cells we lost along the way. There is now evidence that the brain is capable of generating new brain cells even during advanced age.

There is evidence connecting certain metals (e.g., lead, manganese), pesticides (e.g., paraquat, maneb), and solvents (e.g., toluene, trichloroethylene) with neurological symptoms characteristic of Parkinson's disease. Many of the exposures studied have been occupational, and some were acute, rather than lower-level and chronic. Much more extensive research is needed to determine the precise role environmental exposures to these agents may play in prompting Parkinson's disease.[21]

More substantial evidence links various solvent exposures to other neurological conditions, including cognitive impairments, neuropathy, and what is sometimes called "pseudodementia," when temporary neurological dysfunction produces symptoms similar to those of dementia.[22] Organic solvents, including toluene, have also been found to impair color vision, while other solvent exposures have been linked to hearing loss, particularly when combined with noise exposure.[23,24] Such exposures have been primarily studied when they occur occupationally, but some epidemiological studies suggest there is also potential for adverse effects from ambient environmental exposures.[22]

These solvent and pesticide exposures can, of course, occur at any age. But because the neurological disorders with which they are linked mirror those associated with motor and sensory-function declines of aging, they can be mistaken in diagnosis for the effects of aging or diseases of old age like Parkinson's and Alzheimer's diseases.[22,25,26] It also appears that long-term nonacute exposures to solvents and pesticides can affect verbal memory, attention, and spatial skills, with effects that may not become apparent until later in life, when they, too, might be confused with or compounded by aging-related conditions.[22,27]

More subtle environmental exposures are also thought to be implicated in neurological health effects that can manifest later in life. These include exposures to chemicals that may disrupt the normal function of hormones involved in regulating neurological health, chief among them thyroid hormones.

Hormones are intimately involved with neurological function; a normal brain can't develop without healthy thyroid hormone function, and the fetal brain is extremely receptive to thyroid hormone.[28] So if there is early-life thyroid dysfunction, says R. Thomas Zoeller, a professor of biology at the University of Massachusetts Amherst, that person may have cognitive impacts even as an adult.

Thyroid hormones deserve particular attention when considering neurological function in later life because, says Zoeller, these hormones "do different things at different times in the life cycle," all of which are key to maintaining health. Perturbations in the function of these hormones can produce very subtle subclinical effects—effects that a person would not be aware of in their own body—that nevertheless can set the stage for other health effects much later in life.

Weiss says gonadal hormones (i.e., androgens and estrogens) also deserve far more research attention for their influence on neurological function in the elderly.[29] These hormones determine sexual differentiation, but they also are involved in neurogenesis and have demonstrated neuroprotective effects in adult male and female animals.[30]

Although both past and present-day exposures can affect neurological function, staying active physically and mentally could play an important role in preserving and even boosting brain function.

When environmental factors affect thyroid and other hormones, the result can be health effects associated with conditions that impair neurological function. For example, there is evidence that exposure to persistent organic pollutants including dioxins and certain polychlorinated biphenyls, halogenated flame retardants, and pesticides can produce hormonally mediated effects that promote obesity and diabetes, which increase risk for vascular health problems.[31,32] There is also evidence that exposures to some of these same compounds may directly increase risk for hypertension and cardiovascular disease.[31,32] These cardiovascular conditions can, in turn, cause less dramatic neurovascular effects that sometimes result in memory loss, or what's called "vascular dementia," when reduced blood flow to the brain deprives brain cells of oxygen and causes the equivalent of small strokes.[33]

Evidence of similar effects has been reported for exposure to chemicals that are pervasive due to widespread use but are not environmentally persistent. Among these is bisphenol A (BPA). Laura Vandenberg, an assistant professor of environmental health studies at the University of Massachusetts Amherst, explains that numerous animal studies indicate early-life exposure to BPA can produce health effects characteristic of metabolic syndrome.[34] Individuals with metabolic syndrome are at increased risk for hypertension, with its risk for adverse neurological effects. It is also often hard to exercise for those who are overweight or obese or who have cardiovascular disease or diabetes. Yet aerobic exercise in later life appears to be an essential component of maintaining, if not also enhancing, brain function in older age.[35–37]