A study conducted in Brazil by researchers at the University of São Paulo (USP) found that each additional day spent under a heat wave in São Paulo is associated with an increased risk of acute stroke in people aged 65 and older. For the research, a heat wave was defined as at least two consecutive days with maximum temperatures of 33.1 °C or higher.
This impact becomes even more critical when high temperatures are combined with air pollution from fine particulate matter (PM10) – a mixture of microscopic solid and liquid particles originating mainly from the burning of vehicle fuels and inhalable dust, which are highly prevalent in São Paulo’s air. With each additional day under these conditions, the probability of a stroke among older adults in São Paulo increases, according to the research data.
Some preliminary results of the study, conducted as part of a project supported by FAPESP , were presented by Alessandra Carvalho Goulart , a professor at the USP Medical School (FM-USP), in a lecture given during FAPESP Week Netherlands . The event runs through October 29 on the Leiden University campus.
“This is the first time that population-based epidemiological research – that is, research based on real-world data from a large segment of society – has quantified, in Latin America’s largest metropolis, the direct and acute impact of heat stress on the immediate risk of acute stroke in older adults,” Goulart tells Agência FAPESP .
How it was done
To arrive at these results, the researchers used epidemiological data from the Stroke Mortality and Morbidity Study (EMMA), a project also conducted at USP with funding from FAPESP . The goal of EMMA is to assess the epidemiology (the distribution and patterns of diseases in the population), risk factors, incidence rates, survival, and prognosis for more than 1,000 patients diagnosed with ischemic stroke – a type of stroke caused by a blockage in an artery that prevents blood flow to the brain – between 2006 and 2018.
Based on this database, the group analyzed a specific sample of 769 individuals diagnosed with acute stroke, of whom 54.2% were women and 65.5% were 65 years of age or older. Using a statistical model, the researchers compared the weather conditions and air quality to which the individuals were exposed on the days immediately preceding the neurological event. Based on this modeling, the cumulative effect of each additional day of a heat wave was calculated.
In the model that assessed only the thermal impact, an odds ratio (a statistical measure that compares the probability of an event occurring in one group relative to another) of 1.121 was identified. However, when the statistical analysis incorporated the continuous interaction between the heat wave and PM10 concentration, the odds ratio rose to 1.404, demonstrating a substantial 40.4% increase in risk per additional day under this combination of heat stress and pollution.
“Preliminary data from the EMMA study show that climate change and air pollution are not merely distant environmental threats, but immediate urban stressors that affect brain health and trigger acute vascular events in the older population,” says Goulart.
The researcher explains that, physiologically, exposure to intense heat triggers a chain reaction in the body. Thermal overload causes dehydration, which reduces the liquid component of the blood, making it thicker and more viscous. In addition, it causes profound changes in thermoregulation (the body’s ability to control its own temperature) and cardiovascular function. “That set of changes affects blood flow and blood pressure in the body and acts as a direct and immediate trigger for a stroke,” she says.
Protection against brain damage
In parallel with environmental stressors, the researchers assessed how lifestyle habits and cardiovascular care protect the neurological structure against cerebral small vessel disease (CSVD), a condition characterized by changes in the small arteries of the brain that can lead to cognitive decline and dementia.
In studies linked to the Longitudinal Study of Adult Health ( ELSA-Brasil ), the team followed 1,285 participants (61.2% of whom were women aged 66) over four waves of examinations conducted between 2008 and 2024. ELSA-Brasil is the largest epidemiological cohort study in Latin America, conducted by the Ministry of Health and focused on tracking a group of people over time to investigate the incidence and risk factors for chronic noncommunicable diseases, particularly cardiovascular diseases and diabetes.
“We assessed ongoing cardiovascular health using the Life’s Essential 8 score [ a metric created by the American Heart Association that tracks eight key factors: diet, physical activity, sleep, smoking, body mass index, cholesterol, triglycerides, blood glucose, and blood pressure ],” Goulart reports. The results showed that for every 10-point increase in this score, there is a 14% reduction in the risk of developing severe lesions in small cerebral blood vessels.
Brain shield
Regular physical exercise also emerged as a powerful protective shield for cognitive longevity and memory preservation. In a sample of 1,200 volunteers from the ELSA-Brasil study – 59.2% of whom were women aged 66 – the researchers found that maintaining moderate to high levels of physical activity was associated with a 21% to 22% reduction in the risk of exhibiting markers of CSVD. These markers include ischemic lacunes (small scars left by previous cerebral infarcts), microhemorrhages (tiny bleeds in the brain), and perivascular space expansion (swelling in the spaces surrounding the brain’s blood vessels).
“In addition to reducing damage to the cerebral microcirculation, we found that physical activity preserves the volume of the entorhinal cortex, a structure located in the temporal lobe that’s essential for memory processing and spatial navigation,” Goulart notes. The analysis indicated a 21% to 30% reduction in the risk of cortical atrophy (loss of cellular volume) in the entorhinal cortex in both cerebral hemispheres among the most active participants.
To ensure diagnostic accuracy in the ELSA-Brasil study, the team used advanced measurement and neuroimaging technologies. Levels of moderate-to-vigorous physical activity were objectively measured using actigraphy sensors – electronic devices similar to watches that continuously record body movements – worn on the wrist during the third phase of the study (2017–2019).
Neural tissue integrity, meanwhile, was mapped beginning in 2023 using high-resolution brain magnetic resonance imaging. The researchers isolated the effect of exercise from other variables that could influence the results, such as age, sex, race, income, education level, smoking, alcohol consumption, body mass index, hypertension, and diabetes.
“Those findings from ELSA-Brasil demonstrate that cardiovascular prevention and physical exercise are an essential pillar of individual protection for maintaining brain resilience in rapidly aging metropolitan areas,” warns Goulart.
In the researcher’s assessment, the convergence of the EMMA and ELSA-Brasil results highlights that ensuring the quality of life for the older population in contemporary metropolitan areas depends on coordinated actions. These measures have become even more urgent due to the rapid demographic aging in Latin America, as exemplified by São Paulo, where the older population grew by more than 50% between 2010 and 2022 and now exceeds 2 million people.
“Protecting brain health and ensuring longevity in rapidly aging cities requires the implementation of a two-pronged strategy that combines promoting cardiovascular care at the individual level with effective climate adaptation measures in urban centers,” the researcher notes.
According to Goulart, the high prevalence of vascular lesions observed in the examinations points to a significant change in the neurodegenerative profile of the older population. “What we’ve observed in the epidemiological data is a significantly higher prevalence of cerebrovascular events and lesions in the brain’s microcirculation compared to cases of Alzheimer’s disease in that sample.” For the scientist, this finding reinforces the urgency of prioritizing cardiovascular care as the primary line of defense against dementia and cognitive decline in old age.
Neuroprotective effect of lithium
Although epidemiological data indicate a lower proportion of Alzheimer’s disease cases compared to vascular lesions, the search for treatments capable of slowing the progression of this neurodegenerative disease remains at the center of scientific attention. On the therapeutic front, researchers at USP have been investigating the neuroprotective effects of lithium in the treatment of Alzheimer’s disease for more than two decades.
Led by Professor Orestes Forlenza , the group is conducting clinical trials with patients in the pre-dementia stage (who have a condition known as mild cognitive impairment). In these trials, supported by FAPESP , the administration of lithium in subtherapeutic doses (amounts much lower than those traditionally used in psychiatry, thereby minimizing side effects) has demonstrated the ability to mitigate and stabilize memory loss and impaired reasoning.
“We’ve been studying lithium for more than 20 years, and clinical studies have shown its potential to mitigate and stabilize cognitive decline, suggesting that it may alter the course of the disease,” says Forlenza. The researcher also points out that statistical studies comparing the results of multiple independent studies (meta-analysis reviews) have placed the data from the São Paulo group side by side with those from recent pharmacological interventions. “It’s interesting that, with these new anti-Alzheimer’s drugs now on the market, the magnitude of the cognitive-stabilizing effect is very similar to that of lithium,” he notes.
In addition to clinical follow-up, the group’s research on transgenic animal models – mice genetically modified to develop symptoms and brain changes similar to those seen in human Alzheimer’s – has demonstrated that lithium acts directly on the biological and behavioral processes underlying the disease.
Laboratory analyses revealed that the substance, at subtherapeutic doses, helps inhibit processes that disrupt neuronal function, reducing the accumulation of toxic plaques and preventing the destruction of the internal “cytoskeleton” of brain cells. The intervention also demonstrated improvements in anxiety and depression parameters in the animals.
“We’ve demonstrated not only a modification of this biological process, but also an improvement in the behavioral deficits associated with this transgenic model. Lithium restores a function that’s lost due to the pathology of Alzheimer’s disease,” says Forlenza.