Environmental and lifestyle factors play a critical role in shaping cognitive health and the prevalence of neurodegenerative diseases like Alzheimer’s, offering new avenues for prevention and treatment, explained USC University Professor Caleb Finch during the Esther and Isadore Kesten Memorial Lecture on November 22, an annual honor given to a leader in aging research.
In welcoming him to the podium USC Leonard Davis School Dean Pinchas Cohen credited Finch, the school’s first full-time faculty member and the USC Leonard Davis ARCO/William F. Kieschnick Chair in the Neurobiology of Aging, with helping to create the discipline of biogerontology and establish it as a respected field of study. “I cannot think of a more worthy recipient,” said Cohen.
Environmental Improvements Extend Lifespan and Could Lower Dementia Rates
Finch’s lecture emphasized how the prevalence of dementia differed in human groups by interplay between living conditions, including diet and exposure to pollutants, and genetic predispositions. Currently, dementia rates double every six after the age of 60, affecting as many as 20-30% of people by age 100. Much data shows that these dementia rates are significantly lower with environmental and public health improvements.
“Lifespan has more than doubled in the last couple of hundred years, primarily due to the decrease in infection,” Finch said, referencing his collaborative work with USC University Professor and Leonard Davis School colleague Eileen Crimmins. They attribute much of this gain to advancements in vaccination, antibiotics, and public health measures. “Does the dementia rate also change with the environment? The evidence says it does, and it should be much, much lower than what we see today,” he said.
The Complex Biology of Dementia
Finch detailed the pathophysiology of Alzheimer’s disease, the most common cause of dementia, which involves the accumulation of amyloid peptides and tau proteins in the brain. This results in synapse loss and cognitive decline. However, he pointed out that the relationship between these pathological markers and cognitive impairment is far from straightforward.
Highlighting longitudinal studies, Finch reported that less than 50% of cognitive loss is explained by brain pathologies seen in autopsies. “That’s a stunning statement, and it means we don’t know all the right things to look at in the brain,” he said.
Environmental Impacts on Brain Aging
One of Finch’s central themes was the significant role of environmental factors in accelerating or decelerating brain aging. From air pollution to socioeconomic status, these influences shape the trajectory of cognitive decline. “Air pollution and cigarette smoke both accelerate the onset age of Alzheimer’s,” Finch said. “What’s bad for the heart is bad for the brain.”
He highlighted a study with Keck School of Medicine Professor Jiu-Chiuan Chen showing that improved air quality in certain zip codes led to a measurable reduction in dementia rates. “Cognitive status was younger by a year, and episodic memory was younger by a year and a half,” Finch said, emphasizing the potential for public health policies to mitigate cognitive decline.
Finch also drew attention to socioeconomic disparities, noting that individuals with lower education levels and income brackets have a twofold higher risk of Alzheimer’s disease. “It’s not just what we were taught in school. It’s the environment we live in,” he said, citing increased exposure to air pollution, unhealthy diets, and other stressors as factors disproportionately affecting low-income households.
Gene-Environment Interactions
Finch’s research also explored how genetic predispositions interact with environmental exposures. For example, carriers of the ApoE4 gene, a major risk factor for Alzheimer’s, show faster cognitive declines when exposed to air pollution. “This is the first example of gene-environment interactions in air pollution with an outcome for health during aging,” Finch said.
His team further found that female mice exhibited greater gene expression responses to air pollution exposure compared to males, underscoring the need to study sex differences in environmental impacts on brain health.
Lessons from Low-Dementia Populations
Finch presented intriguing findings from studies of the Tsimane people, a forager-farmer community in the Bolivian Amazon. Despite a life expectancy of just 45 years and a high burden of infections, the Tsimane exhibit dramatically lower rates of dementia compared to industrialized populations. “The dementia rate in older Tsimane was 85% lower than in Europe and North America,” Finch shared, attributing this to their minimal exposure to risk factors like air pollution and processed foods, and greater physical activity.
Historical records also suggest that dementia may be a relatively modern phenomenon. Finch and historian Stanley Burstein, a professor emeritus at Cal State LA, found that ancient physicians wrote of ailments like frailty, broken bones, and movement difficulty but there’s nothing suggestive of a general cognitive impairment at later ages.
Promising Interventions and Future Directions
Finch expressed cautious optimism about emerging treatments for Alzheimer’s disease, including iron chelation therapy and the class of GLP-1 receptor agonists originally developed for diabetes. However, he noted that new therapies, like antibody treatments, often come with severe side effects.
“There’s a lot more work to be done,” Finch concluded, emphasizing the need for a holistic approach that combines innovative basic research, environmental interventions, and public health initiatives. “Slowing dementia is possible,” he said.
The Esther and Isadore Kesten Memorial Lecture was established in 1973 by Alan Davis, son of Sophie and Leonard Davis, in memory of his grandparents. The funds from this endowed lectureship allow the USC Leonard Davis School to annually honor an individual whose research in gerontology has contributed significantly to the understanding of the aging process.
