More links are emerging between loneliness and how the brain processes feelings of reward. In mice, loneliness sensitises certain midbrain neurons to a neurotransmitter called dopamine, which can also cause people to cave in to cravings, such as for food and drugs. Likewise, isolation might make humans more sensitive to rewards and more eager to seek them out.

In 2023, Tomova and her colleagues published a preprint for a study in which they isolated adolescents from social contact for up to four hours. After isolation, participants were offered the chance to earn a monetary reward. The isolated participants agreed more quickly than did those who were not isolated, suggesting that isolation had made them more responsive to rewarding actions.

Although research on dopamine and loneliness is still emerging, scientists have also long recognised the connection between loneliness and another type of chemical signal – stress hormones called glucocorticoids. Humans need some level of glucocorticoids “to function; to wake up”, says neurophysiologist John-Ioannis Sotiropoulos at the National Centre for Scientific Research ‘Demokritos’ in Athens. But persistent loneliness leads to chronically high levels.

These chemicals could provide a link between loneliness and dementia. In a mouse model of Alzheimer’s disease, for example, glucocorticoids increased the levels of two proteins that are involved in the main hallmark of the condition, the protein plaques that tangle around neurons and interfere with memory and cognition.

Stress is an extra assault on brains that are already wearing out as people get older, Mwilambwe-Tshilobo says, but she wants to see more research before committing to an opinion on exactly what part stress-related chemicals play in neurodegeneration. “It could accelerate the rate of ageing, but there hasn’t been work that explicitly looks at that,” she says.

Tomova says that although high levels of stress hormones probably contribute to dementia, it’s also likely that people who feel lonely miss out on the mental exercise that social interactions provide. And just as a muscle needs exercise to stay fit, so does the brain. In fact, loneliness has been associated with a smaller volume of grey matter in the brain.

“This is all hypothesis, really, at this stage,” Sommerlad says, but the idea is that socialising maintains neural connections that might otherwise be lost.

Researchers looking for the neural signature of loneliness have also found differences that could help to explain some of the correlations between loneliness and dementia. Previous research has suggested that there are changes in the connectivity between brain areas in people who feel lonely A 2020 study examined an area of the brain called the default network – so called because it’s active by default when a person isn’t engaged in a particular task and turns their attention inward – in older people who reported being lonely.

Previous work had suggested that young people who feel lonely have high neural cross-talk between the default network and other networks associated with vision, attention and executive control13, possibly because they’re on high alert for social cues, says Spreng, one of the authors on the 2020 study of older people. But his team found the opposite in brain scans from the UK Biobank cohort of people aged 40 to 69. Loneliness weakened connections between the default network and the visual system and instead strengthened connections within the default network.

That could be because older people remedy loneliness by retreating into memories of past social experiences, Spreng says. In doing so, they strengthen the default network.

The default network is one of many networks in the brain that accrues damage during Alzheimer’s disease. Spreng and his colleagues are investigating whether strong default networks can indeed be linked to neurodegeneration – and if so, why. He wonders whether robust neural connections might allow pathologies to spread more readily in the network. The idea is far from proven, but it’s a plausible explanation and “an interesting hypothesis”, says cognitive neuroscientist Anastasia Benedyk at the Central Institute of Mental Health in Mannheim, Germany.

The study “lays the foundation for us to be able to test some hypotheses a little bit more empirically”, says Mwilambwe-Tshilobo, who was also involved in the work linking the default network with loneliness.

Some remedies for loneliness will come as no surprise. Increasing access to social activities, for example by housing people in communities with common areas, can help, Sommerlad says. Some researchers are also finding ways to tap into the neural mechanisms underlying loneliness directly, through exercise, for instance.

Walking 4-5 kilometres over the course of an hour completely reversed feelings of low mood associated with loneliness in some people, Benedyk and her colleagues found. What’s more, people with high connectivity in their default networks – the same area Spreng studied, which is also known to be affected by depression – were among those who benefited from exercise the most.

One possible explanation for this observation is that people with depression are “stuck in rumination” – a behaviour that draws heavily on the default network, Benedyk says. Exercise could force them to use other parts of their brain by interrupting neural processes that are associated with self-reflection and shifting activity to areas associated with physical activities – freeing them from a cycle of negative thoughts.

Exercising is also a great excuse to socialise. These days, Chaklos is retired, but she now leads the Boston branch of a US programme called ‘Walk with a Doc’ in which physicians invite community members to walk with them. At the group’s February walk, about 14 people chatted and strolled inside the Prudential Center Mall in Boston, Massachusetts, where they could avoid New England’s winter weather. The activity “just uplifts a person’s mood”, Chaklos says. “Even if you’re still going back home to be by yourself, you don’t feel totally alone anymore.”

• A Nature report