LONDON — Long-term exposure to outdoor heat was associated with a blood biomarker profile consistent with early Alzheimer’s Disease (AD) pathology — but only in women — preliminary research suggests. 

Among older women, higher heat exposure over 5 years was associated with lower amyloid-beta42/40 ratios and higher phosphorylated tau 181 (p-tau181), but not with neurofilament light (NfL) or glial fibrillary acidic protein (GFAP), biomarkers of more generalized neuronal and astrocytic injury. No such associations were observed in men.

“Recurrent heat exposure may not only increase acute clinical outcomes like heat stroke but also shape the biological context where AD pathology can develop, particularly in older women and even before there’s evidence of generalized neuronal injury,” lead investigator Eun Young Choi, PhD, of the Leonard Davis School of Gerontology at the University of Southern California, Los Angeles, told Medscape Medical News.

The findings were presented on July 13 at the Alzheimer’s Association International Conference (AAIC) 2026.

A Growing Problem

As a result of global warming, exposure to extreme heat is becoming more common. An estimated 85% of the worldwide population experiences at least 30 days of strong heat stress (≥ 90 °F) annually.

Growing epidemiologic evidence suggests exposure to extreme outdoor temperatures may increase the risk for cognitive decline and dementia, while animal studies have linked heat stress to AD-related processes such as altered amyloid processing, tau phosphorylation, and neuroinflammation. Whether these biologic effects are reflected in blood biomarkers of AD pathology in humans, however, has remained largely unexplored, said Choi.

To investigate this question, the investigators examined whether long-term outdoor heat exposure was associated with blood biomarkers of AD pathology and neurodegeneration in a large, population-based sample of older US adults.

The study included 3668 predominantly White older adults (1553 men and 2115 women; mean age, 69 years) from the 2016 Health and Retirement Study, a large, nationally representative cohort that has followed US adults aged 50 years or older every 2 years since 1992. Blood-based neurodegenerative biomarkers were first collected in 2016.

To estimate long-term heat exposure, the researchers used gridMET, a nationwide gridded climate dataset, to calculate each participant’s mean warm-season (April-September) heat index — a measure that combines air temperature and relative humidity — during the 5 years before blood collection.

Choi noted that amyloid-beta and p-tau181 are considered the core biomarkers of AD because they directly reflect disease pathology. By contrast, NfL and GFAP are markers of neuronal injury and astrocyte activation, respectively, and can be elevated in a range of neurologic disorders, including stroke, traumatic brain injury, and AD.

At baseline, women had significantly higher GFAP levels than men (111.88 pg/mL vs 87.97 pg/mL) but lower p-tau181 concentrations (1.85 pg/mL vs 2.22 pg/mL; P < .001 for both).

Women had significantly higher GFAP levels than men (111.88 pg/mL vs 87.97 pg/mL) but lower p-tau181 concentrations (1.85 pg/mL vs 2.22 pg/mL; P < .001 for both).

Choi and colleagues analyzed the association between long-term heat exposure and each biomarker separately in men and women. Heat exposure was modeled per IQR increase in the 5-year mean warm-season heat index, equivalent to a 14 °F difference (75 °F to 89 °F).

Models were adjusted for sociodemographic, behavioral, and clinical factors, including race and ethnicity, education, smoking, alcohol use, physical activity, obesity, cardiovascular disease, stroke, diabetes, and APOE epsilon 4 carrier status.

Results showed men and women had similar long-term heat exposure, with mean 5-year warm-season heat index values of 80.79°F and 80.97°F, respectively.

Heat exposure was not significantly associated with any of the biomarkers in men. In women, it was not associated with NfL or GFAP, but each 14°F increase in the 5-year mean warm-season heat index was associated with a lower amyloid-beta42/40 ratio (beta = -0.02; 95% CI, -0.04 to -0.01; P = .005) and higher p-tau181 levels (beta = 0.06; 95% CI, 0.01-0.10; P = .017) after adjustment for potential confounders.

The study showed men and women had similar 5-year mean warm season heat index exposure (80.79 °F vs 80.97 °F).

Why Are Women More Vulnerable Than Men?

There are several reasons why women may be more cognitively susceptible to excessive heat. For one thing, they’re built differently than men so the same outdoor heat may not translate into the same internal physiologic burden.

Choi said several biologic differences may make women more susceptible to the effects of extreme heat. When air temperatures exceed skin temperature, the body depends on sweat evaporation to dissipate heat. Because women generally produce less sweat than men, their cooling capacity is reduced, allowing more heat to be retained and core body temperature to rise more quickly.

She said the effect may be even greater after menopause, when aging and declining estrogen levels further impair sweating, blood flow to the skin, and vascular regulation.

When air temperature exceeds skin temperature, the body depends on sweat evaporation to dissipate heat. Because women generally produce less sweat than men, they may retain more heat.

“More heat is therefore stored in a woman’s body, so core body temperature may rise more quickly than in men,” Choi said.

She added that the effect may be amplified after menopause because aging reduces sweating and the ability to redirect blood to the skin, while declining estrogen levels may further impair vascular dilation and fluid regulation.

Choi said greater internal heat strain may make the female brain more vulnerable by disrupting cerebral blood flow regulation. Experimental evidence also suggests women may be more susceptible than men to heat-related acceleration of AD pathology.

The study did not account for access to or use of air conditioning, an important limitation, Choi said. Although the analyses adjusted for income, that does not necessarily reflect whether people can effectively cool their homes. She noted that in Phoenix, some residents have died during extreme heat despite having air conditioning because they could not afford to use it.

The study also lacked data on participants’ occupational histories, making it impossible to assess whether those with prolonged outdoor work exposure are more susceptible to the effects of heat. Choi said the team hopes to explore that question in future research.

She added that the findings support considering heat exposure as a potential risk factor for dementia. She emphasized that, unlike many risk factors, heat exposure is largely preventable through simple measures such as limiting outdoor activity during extreme heat and staying well hydrated.

“I find many older adults don’t necessarily know that they have to avoid outdoor activity and drink a lot of water when it’s hot, so this basic thing should be emphasized more.”

Timely, Relevant Research

The findings are “compelling,” and particularly timely as extreme heat events become more common worldwide, said Courtney Kloske, PhD, director of scientific engagement at the Alzheimer’s Association, who was not involved in the research.

However, she cautioned that it is too early to incorporate heat exposure into routine dementia risk assessments. Although the study showed an association between long-term heat exposure and AD-related biomarkers in women, it does not establish that heat causes those biologic changes or increases dementia risk, she said.

“Additional research is needed to clarify the relationship and underlying mechanisms,” Kloske added.

Physicians should continue to focus on evidence-based strategies to reduce dementia risk, including managing cardiovascular risk factors and encouraging regular physical activity, a healthy diet, adequate sleep, and social and cognitive engagement, Kloske said.

The study was supported by the National Institute on Aging of the National Institutes of Health and by the Alzheimer’s Association. The investigators and Kloske reported having no relevant financial disclosures.