Symptoms of early dementia reversed by bespoke treatment plans

A personalised programme that combines targeted medical interventions with lifestyle changes seems to improve memory and functioning among people with mild cognitive decline or the early stages of dementia. This involves assessing someone for factors that could be affecting their cognition – such as mould exposure, infections or hormonal deficiencies – and creating a bespoke plan to target them.

Dementia is an umbrella term for several conditions that affect memory, thinking and the ability to perform daily activities. It has no cure, with treatment generally focusing on relieving symptoms. But for Alzheimer’s disease – which makes up about 60 to 70 per cent of dementia cases – some drugs, like lecanemab, can clear the sticky protein plaques that form in the brain and are thought to contribute to the condition.

However, many have argued that these don’t improve people’s symptoms in a meaningful way. This may be due to the complexity of Alzheimer’s and other forms of dementia, which, evidence increasingly suggests, involve age-related changes in the brain as well as genetic, health and lifestyle factors. “[Patients] didn’t get well because we weren’t treating what was causing it in the first place,” says Kat Toups at Bay Area Wellness, a private practice in Walnut Creek, California.

Now, she and her colleagues have investigated the potential of bespoke treatment plans. “The approach is: let’s find all the things that are hurting the brain [and] get rid of those,” says Toups. “Then let’s put back in whatever the brain and the whole body is needing as far as nutrients and hormones, and then let’s do things for neuroplasticity to help regain your brain.”

The team recruited 73 people – aged 65, on average – with mild cognitive impairment or early-stage dementia. “Some of them met [the] criteria for Alzheimer’s and others for MCI [mild cognitive impairment],” says Toups.

They all underwent testing to identify potential contributors to their symptoms. Alongside blood tests to look for biomarkers of Alzheimer’s, the researchers assessed their levels of inflammation and checked whether they had any underlying infections or hormonal, nutritional or microbial-related deficiencies. Using this information, the researchers created personalised treatment plans for 50 of the participants, such as addressing nutritional deficiencies via supplements.

They were also told to adopt a plant-rich diet, do aerobic and strength training six days a week, and complete daily cognitive training via games that targeted their memory, attention and visual-processing speed. This group was also given tips to optimise sleep and manage stress.

The remaining 23 participants continued with their usual treatment and lifestyle habits.

After nine months, those in the personalised group saw their overall cognitive score – assessed by CNS Vital Signs, a standard computer-based cognitive test – improve by 13.7 points, compared with a decline of 4.5 points in the standard-care group. Improvements were also seen across specific domains within the test, including memory (up by 10.6 points versus a decline of 2.7), executive function (up by 9.8 versus down by 2.2) and processing speed (up by 6.9 versus down by 1). “Over 90 per cent of the patients in the precision-medicine approach had statistically significant improvements,” says Toups.

Ana Daugherty at Wayne State University in Detroit, Michigan, says the findings are promising and reflect a growing effort to address the many known and suspected risk factors for poor cognition in a personalised way. “The precision-medicine approach can incorporate the many health and genetic risk factors and lifestyle resiliency factors that we’ve identified as a field over the last several decades.” However, she adds that the results need to be confirmed in larger studies.

Earlier evidence on the potential of personalised medicine was largely based on case reports, with little data from randomised-controlled trials. “This trial provides the most rigorous evidence to date,” says Christin Glorioso at NeuroAge Therapeutics, a biotech company in San Francisco.

However, blood biomarkers and signs of dementia on brain scans didn’t change from the start to the end of the study in either group. Andrew Surmak, an independent imaging scientist in Baltimore, Maryland, says it can be difficult to gauge the impact of an intervention on the trajectory of a condition in a small group over a short time. “In many cases, improvements may reflect changes in functional or cognitive measures rather than true modification of underlying neurodegenerative pathology.”

It is also unclear to what extent the participants benefitted from the personalised interventions versus the lifestyle changes like doing regular exercise and cognitive training, which have repeatedly been linked to a reduced risk of dementia. “Separating their individual contribution becomes very difficult, especially when interventions are layered and individualised,” says Thomas Holland at Rush University in Chicago. “In most cases, it is likely the cumulative effect that matters most, rather than a single isolated component.”

Glorioso says future trials could blind the participants to certain aspects of their intervention, such as whether they received supplements or a placebo. “The unblinded design, largely negative biomarker findings and inability to attribute effects to specific interventions leave important questions unanswered.”

But Toups believes these interventions should be implemented quickly. The control group was offered six months of personalised interventions and lifestyle advice after the study ended, she says. These results, which haven’t been published, suggest they didn’t improve as quickly as those who started earlier, she says. “The delay [is] hurting them. There’s no time to waste when your brain is degenerating.”