Donanemab and seven other breakthroughs for Alzheimer’s and dementia in 2023

US pharmaceutical company Eli Lilly has announced promising results for its experimental drug donanemab, which has been shown to slow cognitive decline in Alzheimer’s patients.

The Indianapolis-based firm has claimed that donanemab “significantly slowed cognitive and functional decline in people with early symptomatic Alzheimer's disease”. Eli Lilly said that those with mild Alzheimer’s in its 1,736-person clinical trial “showed 35% less clinical decline than did those who received a placebo”.

The results are similar to those of lecanemab, a drug made by US company Biogen and Eisai in Tokyo, which was approved by the US Food and Drug Administration (FDA) in January.

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Donanemab targets amyloid protein, which is believed to cause dementia by accumulating in the brain and damaging neurons. The trial results provide strong evidence that amyloid is a key driver of Alzheimer’s disease.

But researchers have warned that questions remain “as to the drug’s clinical usefulness, as well as whether the modest benefit outweighs the risk of harmful side effects”, said Nature. In the clinical trial, three deaths were reported among people taking the drug, two of which were attributed to adverse events such as brain swelling or microhaemorrhages.

The results have been described as “transformative in an enormously important way from a scientific point of view” by Jeffrey Cummings, a neuroscientist at the University of Nevada Las Vegas. “They’re terrific,” he told Nature.

Others, however, are more cautious. Neurologist Marsel Mesulam, at Northwestern University in Chicago, stated that “clinically, their significance is doubtful” and that the modest effect suggests factors other than amyloid contribute to Alzheimer’s disease progression. Eli Lilly plans to file for approval by the FDA by the end of June based on these results.

The experimental drug is just one of the many scientific breakthroughs that offer hope in the fight against Alzheimer’s and dementia in 2023.

1. Gene therapy

A new gene therapy for Alzheimer’s has been found to significantly lower levels of the tau proteins that are thought to cause the disease. In a Phase 1b trial involving 46 patients, the drug BIIB080 (MAPTRx) – which was injected into the nervous system via the spinal cord – was found to be safe and well tolerated, in a study published in the journal Nature.

It’s not yet clear if it improves the clinical condition of Alzheimer’s patients, but it did cut levels of tau by 50%, on average, by silencing the messages from DNA that create abnormal tau proteins within cells. Further trials will be needed to show if this actually leads to a clinical benefit, reports The Daily Telegraph, but it raises hopes of a treatment to slow or even reverse the development of Alzheimer’s.

2. Sleeping pills

In a study published in March in the Annals of Neurology, people who took a sleeping pill before bed had lower levels of the amyloid beta protein that builds up in the brains of Alzheimer’s patients. Poor sleep has been linked to the condition.

However, the scientists, from Washington University School of Medicine, St Louis, stressed that the research was in its early stages, and said that it was too soon to recommend that people with insomnia take sleeping pills to reduce the risk of Alzheimer’s.

The drug used in the study was suvorexant. It is used in the US under the brand name Belsomra, but it has not been approved for use in the UK.

3. Hearing aids

Middle-aged adults who notice they are losing their hearing should immediately start wearing hearing aids to reduce their risk of dementia, a study published in The Lancet suggested.

Drawing on data from the UK Biobank, researchers in China studied 438,000 adults who had an average age of 56. One in four reported some level of hearing loss as they grew older, and these people were 42% more likely than the others to be diagnosed with dementia.

But wearing a hearing aid eliminated this increased risk. It is thought that wearing the aids helps maintain connections between brain cells, while also preventing other negative effects of hearing loss such as reduced social interaction.

Previous studies have suggested that hearing “may account for about 8 per cent of the potentially modifiable risk of developing dementia”, The Times reported, yet in the UK, about 80% of people experiencing hearing loss do not use hearing aids.

4. Mediterranean diet

Eating a Mediterranean diet – rich in whole grains, nuts, fish, vegetables and fruit – can substantially reduce the risk of dementia, researchers have found.

Their findings, published in the journal BMC Medicine, are based on analysis of data on more than 60,000 people from the UK Biobank (most of whom were of European ancestry), who had completed a survey about their eating habits. The researchers scored individuals according to how closely they followed a Mediterranean diet, and noted their genetic risk for dementia.

Over the course of nearly a decade, there were 882 cases of dementia, but those who followed a strict Mediterranean diet had a 23% lower risk of developing the condition than those who did not, and this did not seem to be affected by their genetic risk.

The researchers, from Newcastle University, conclude that advice to eat a healthy, largely plant-based diet could be incorporated into future strategies for preventing dementia. However, other experts pointed out that it is quite likely that people who eat healthily have a more healthy lifestyle overall, making the impact of their diet hard to assess.

5. Healthy hearts

People with healthy hearts in middle age are likely to live significantly longer without conditions such as cancer and dementia than those whose heart health is poor, a study has indicated.

Researchers from Tulane University in the US analysed more than 135,000 participants in the UK Biobank project, whose heart health had been scored according to various measures, including diet, body mass index, cholesterol levels, blood sugar and blood pressure.

Their preliminary findings were that the women who’d had the highest scores aged 50 could expect to live another 33 disease-free years, on average – nine more than those with the lowest score. For men, the difference was about seven years. And even the majority of participants who only achieved intermediate scores for heart health were likely to be free of chronic illness for markedly longer than those with low scores – six years for women and four for men.

Separately, a review of existing research on the impact of exercise on health found that if everyone were to be physically active for just 11 minutes a day, one in 20 cases of cardiovascular disease would be prevented, along with nearly one in 30 cases of cancer.

6. Vitamin D

Taking vitamin D tablets may help stave off dementia in older people, a study has found.

Previous research has shown that vitamin D plays a role in clearing the brain of the amyloid plaques that are a hallmark of Alzheimer’s; but studies into whether taking supplements can ward off the disease have had conflicting results.

To explore this further, scientists at the University of Exeter looked at almost 12,400 American adults with an average age of 71 who were followed for ten years. During this time, 2,696 of them were diagnosed with dementia. At the start, 37% of the participants were regularly taking vitamin D – and the members of this group were 40% less likely to be diagnosed with the condition than the rest of the cohort.

The vitamin’s apparently protective effect was particularly marked in women, possibly because declining levels of oestrogen during menopause can make it harder to produce the vitamin. Its effects were also significantly greater in people who did not carry the APOE4 gene, which is associated with an elevated risk of Alzheimer’s. The researchers speculate that people with this gene absorb vitamin D better in the intestine, which might reduce the impact of the supplements.

7. Hormone replacement therapy

HRT might offer some protection against Alzheimer’s in women who carry a genetic variant that increases the risk of disease.

Researchers at the universities of East Anglia and Edinburgh studied data on 1,178 women who’d signed up to the European Prevention of Alzheimer’s Dementia initiative. All were over 50 and dementia-free when they joined the study, which tracks brain health over time.

The study revealed that in women carrying the APOE4 gene, using HRT was “associated with better memory and larger brain volumes”, said Dr Rasha Saleh of the study team. The associations were particularly evident when the women had started taking HRT early, during perimenopause.

The researchers stressed that more work is needed to confirm a link with Alzheimer’s, but cognitive performance and lower brain volumes are predictors of future dementia. “It’s too early to say for sure that HRT reduces dementia risk in women,” they said, “but our results highlight the potential importance of HRT... in reducing Alzheimer’s risk.”