A cognitive “speed training” game that cuts dementia risk by 25 per cent alters levels of beta-amyloid, a protein that clogs up the brain in Alzheimer’s disease, in men, but not in women.

It is the first time brain training has been shown to influence the levels of a neurodegenerative marker, strengthening the evidence suggesting that mental exercises can boost brain health.

“One of the main markers that’s indicative of future dementia risk got better for men who completed cognitive speed training,” says  at Clemson University in South Carolina, who presented the research at the Alzheimer’s Association International Conference in London on 12 July.

The computer-based speed training involves recalling where objects have flashed up, with the task becoming harder as performance improves. A prior 20-year study by some of Chai’s colleagues showed that people aged 65 and older, who did the training were 25 per cent less likely to be diagnosed with Alzheimer’s disease or a related form of dementia compared with a control group.

In the latest study, Chai and her team recruited a separate group of 53 people from the US aged 65 and older, 13 of whom were male. About a third of the participants were asked to complete between 2 and 4 hours of speed training each week for 4.5 months.

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The remaining participants were either told to spend the same amount of time playing games such as Solitaire, word search and a game similar to Connect 4, or to complete another kind of brain training in which they had to strategically track objects and switch between tasks.

To explore how speed training may reduce dementia risk, the team collected blood samples from all of the participants at the start and end of the training period.

This revealed that, among men, speed training increased the ratio of two forms of beta-amyloid found in the blood, which suggests the training boosted the brain’s ability to clear beta-amyloid 42. This protein forms clumps called plaques in the brain during Alzheimer’s disease, disrupting brain function. The other two kinds of training had no effect.

“It’s a really cool finding,” says  at McGill University in Montreal. “It is definitely strengthening what they’ve [previously] shown with the reduction in dementia.”

Some Alzheimer’s treatments, such as lecanemab, have been designed to help clear amyloid from the brain, but they only marginally slow cognitive decline during Alzheimer’s disease. The limited benefit seen in trials is probably down to these treatments being taken at a relatively late stage of the condition, when substantial brain damage has already occurred, says at University College London.

Engaging in cognitive training to reduce beta-amyloid build-up before dementia develops may have a bigger effect on dementia because it would be done before much brain damage has occurred, says Castegnaro.

However, cognitive training had no effect on amyloid levels in female participants in the study. This suggests that speed training reduces dementia risk in different ways in women and men, says Chai.

The team hopes to explore how speed training may benefit women in future studies, says Chai. But first, the findings need to be verified in geographically and ethnically diverse groups, says Novozhilova.

A combination of two drugs used to treat hay fever and psychosis cooled down the core body temperature of mice and monkeys, reducing brain damage after a stroke. These medications have also undergone preliminary testing in people, and will now be evaluated in a follow-up clinical trial.

Researchers have spent decades investigating ways to chill people’s brains after they have a stroke to try to limit the damage. The idea is to freeze brain cells in a hibernation-like state so they don’t need as much oxygen and glucose when a stroke cuts off their blood supply. If brain cells can be kept alive until blood flow is restored, for example, by removing a clot, a patient may be spared from extensive brain damage and related speech and movement problems.

Unfortunately, the physical cooling strategies that have been looked at so far – including cooling blankets, ice packs and helmets – haven’t worked well. This is because they cause intense discomfort and uncontrollable shivering, says at the University of Newcastle in Australia, who wasn’t involved in the study.

Shivering is one method the body uses to “fight the induction of hypothermia”, making it hard to get body temperature down low enough, she says. “It’s great to see different cooling therapies being tested out for stroke because we know that physical cooling is just not feasible,” says Coupland.

Shuaili Xu at Capital Medical University in Beijing, China, and his colleagues administered the two drugs, promethazine and chlorpromazine, which have been known to reduce body temperature , to mice and rhesus monkeys following induced strokes.

In both animals, the drug combination led to drops in core body temperature, suppressed glucose metabolism in cells and lessened the amount of brain damage caused by the stroke. The reduced brain damage also meant the treated monkeys displayed better use of their limbs.

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Next, the team conducted a clinical trial involving 32 people who had just had a stroke. Upon hospital admission, the subjects were given the promethazine and chlorpromazine combination or a placebo, in addition to standard clot-removal therapy.

The promethazine and chlorpromazine treatment only reduced the patients’ body temperature by 0.3°C (about 0.5°F) and did not reduce stroke damage. However, Xu thinks this is because the infusions were done over 12 hours, which was too slow to bring down core body temperature by a meaningful amount. “It might have led to a low blood drug concentration per unit of time,” he says.

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His team is now launching another trial to see whether faster infusions over an hour produce stronger cooling effects and therapeutic benefits. “The fact that they’ve proven that it’s safe and these drugs are already used in humans for other indications means I think that it’s reasonable to proceed with further clinical trials,” says Coupland.

Promethazine and chlorpromazine are known to be relatively safe because they have been used for decades. Promethazine is a sedating antihistamine that can ease hay fever and assist sleep, while chlorpromazine is an antipsychotic drug used in the management of schizophrenia and bipolar disorder. They both act on the central nervous system to reduce core body temperature, without translating into shivering or subjective feelings of coldness.