select search filters
briefings
roundups & rapid reactions
Fiona fox's blog
A study published in Gut Microbes looks at dietary and gut-derived metabolites predicting early cognitive decline.
Prof Fiona Carragher, Chief Policy and Research Officer at Alzheimer’s Society, said:
“Blood tests could transform how we diagnose dementia and even identify a person’s risk of developing dementia in the future. Studies like this are helping to build a clearer picture of the early biological changes linked to the condition.
“This is a small study looking at associations at a single point in time, so we cannot say whether these changes cause cognitive decline or are a result of it or whether these individuals went on to develop dementia. It does, however, add to a growing field of research looking at the connection between gut and brain health.
“Understanding risk earlier could be key to helping people access support, take steps to reduce their risk, and take part in research. Alzheimer’s Society part funded the influential Lancet Commission on dementia prevention, intervention and care, which identified 14 modifiable risk factors for dementia and showed that up to 45 per cent of dementia globally may be preventable.
“Dementia is one of the biggest challenges facing our health and care system, and with the number of people affected set to rise to 1.4 million by 2020, prevention must be a central part of how we tackle it.”
Dr Sheona Scales, Director of Research at Alzheimer’s Research UK, said:
“Growing evidence suggests that changes to bacteria in the gut may be linked to dementia risk. This interesting study identifies chemicals in the blood linked to gut bacteria that are associated with the earliest stages of memory and thinking problems. While current blood tests for Alzheimer’s work by detecting levels of specific proteins linked with the disease, this research may offer a new avenue for future blood-test development.
“This study can’t say whether people with early memory and thinking problems will go on to develop dementia, but it identifies an interesting area for further research. Given the study involved a relatively small group of people, larger and longer-term studies are needed to build on these findings and understand whether this type of test could be used alongside existing ones.
“As we continue growing the types of tests available, more people will be able to receive an accurate diagnosis earlier, helping them access future treatments. Alzheimer’s Research UK is committed to funding studies like this, which could give doctors more tools to diagnose dementia and ultimately bring us closer to a cure.”
Prof Eef Hogervorst, Professor of Biological Psychology, Loughborough University, said:
“This is a rather small study, with 50 controls, 50 people with subjective memory complaints (SMC) and 50 people with objective memory and other cognitive issues, called mild cognitive impairment (MCI, who did not have dementia). The MCI as a group is thought to be at risk for dementia, but many of these people do not convert to dementia and in some studies about a quarter initially diagnosed as MCI is seen to return to control level cognitive function over time.
“The authors matched these groups for age (on average 65 years of age), body mass index (BMI) and sex and people had to be healthy overall. According to the authors: ‘Participants were excluded if they had a history of significant neurological, psychiatric, gastrointestinal, or metabolic disorders (e.g., diabetes mellitus, liver disease), chronic fatigue syndrome, or gall bladder abnormalities, were current or recent smoking, alcohol or drug dependent, used medications or supplements known to alter gut microbiota (e.g., antibiotics, probiotics, prebiotics, symbiotics, fish oil, or high flavonoid intake, defined as >15 portions/day) within four weeks of sample collection or with clinically significant depression or anxiety. Individuals taking antidepressants, antipsychotics, anticoagulants (e.g., warfarin), or any medication affecting gastrointestinal function or with gastrointestinal symptoms such as diarrhoea at baseline were also excluded’.
“As around 17-20% of older people suffer from depression (which can affect the gut microbiota and cognitive performance), and many older people will have other morbidities/other factors resulting in exclusion from the study, this may not be a particularly representative group of older (control) people. This is fine when deciding to focus on the microbiome and exclude most factors that can influence this but makes the study perhaps less suitable for diagnostics in the general population as surmised by the authors.
“Memory tests were not included in the analyses, but there were some differences in the more complex forms of information processing between groups, mainly in working memory (digit span backward).
“The authors selected people into macro food groups (intake of calories, carbohydrates, protein, fats, water, alcohol, vitamins and minerals categorised people as low, moderate or high intakes of macronutrients within these groups) to control for background diet in the analyses.
“Analyses further controlled for age, BMI, sex (even though these were all already matched for), but also albumin, kidney function, and liver function (but not bilirubin or blood glucose, even though these were significantly different between groups). Lower bilirubin (as seen in the SMC and MCI), a marker of metabolic dysfunction, has been associated with higher blood glucose levels and insulin resistance.
“The results showed that six metabolites produced or associated with gut microbiota (5 hydroxyindole acetic acid, indole-3-propionic acid, choline, indoxyl sulfate, kynurenic acid and kynurenine) showed good distinction between the groups and the authors suggested these could be used as early markers of cognitive decline.
“The main issue is that the study did not look at cognitive decline. It looked at three groups who had different cognitive performance, but that could be due to many factors. For instance, physical activity was not controlled for in analyses which can affect gut microbiome and cognition, nor did the analyses control for differences in dietary individual components which could be responsible for the associations found.
“For instance, blood glucose was higher by each group, so despite excluding people who knew they had diabetes, some people may have had higher blood glucose levels than they realised. Leaky gut, allowing inflammatory toxins to enter the blood, can create low grade inflammation which can increase insulin resistance and via this mechanism affect dementia risk. Leaky gut is seen in people with high fat/sugar diets, use of NSAIDS, excessive alcohol use, infections and inflammatory bowel disease. These factors were not all controlled for in analyses.
“This could also be the case for other preclinical or relatively symptom free morbidities which could have been associated with both gut and issues in more complex information processing without one necessarily affecting the other. For instance, gum disease affecting the gut is common in older people and is associated with dementia, but this is thought to occur via its effect on pro-inflammatory cytokines. Problems with gums can also lead to poor nutritional intake affecting gut microbiome.
“It is an interesting finding and a very well written paper with good theory and impressive statistical analyses, but with small groups and no follow-up I think the conclusion that this can be an early diagnostic marker for cognitive decline and even dementia may be a little overstated.“
‘Circulatory dietary and gut-derived metabolites predict early cognitive decline’ by Emily Connel et al. was published in Gut Microbes at 00.01 UK Time on Wednesday the 1st of April 2026.
Declared interests
Prof Fiona Carragher: “Alzheimer’s Society funds dementia research, including work on early detection and diagnosis such as the Blood Biomarker Challenge. Fiona Carragher has no personal financial interests to declare.”
Dr Sheona Scales: “Alzheimer’s Research UK has funded this study.”
Prof Eef Hogervorst: “Eef Hogervorst did consultancy for Proctor and Gamble on nutrition and in the past for NESTEC and Sandoz. She was funded for nutrition and brain research by ARUK, ISPF, British council/Newton trust and ESRC and acted as dementia expert for NICE and ESHRE guidelines.”