Mounting evidence suggests that the 'gut-brain axis' is implicated in various aspects of health and disease.
While the cause of IBD is not clear, it is thought to develop from an impaired immune response to changes in the gut microbiome. A recently published large population-based study suggests that IBD may have a role in the development of the neurodegenerative disorder, Parkinson's disease. But it's not clear if IBD may also be linked to a heightened risk of dementia.
To explore this further, a collaborative team of researchers from Taiwan and the USA, drew on data for 1,742 people aged 45 and above who had been diagnosed with either ulcerative colitis or Crohn's disease between 1998 and 2011 registered with the Taiwan National Health Insurance programme.
Their cognitive health was tracked for 16 years following their IBD diagnosis and compared with that of 17,420 people who were matched for sex, age, access to healthcare, income, and underlying conditions, but who didn't have IBD.
The results, published in the journal Gut, show that during the monitoring period, a larger proportion of those with IBD developed dementia (5.5%), including Alzheimer's disease, than those without (1.5%).
Additionally, people with IBD were diagnosed with dementia an average of 7 years earlier (76) than those without IBD (83).
After taking account of potentially influential factors, including age and underlying conditions, people with IBD were more than twice as likely to develop dementia as those without.
Of all the dementias, the risk for Alzheimer's disease was greatest: those with IBD were six times as likely to develop this as were those without IBD.
Neither sex nor type of IBD had any bearing on the findings. But the risk of dementia seemed to be associated with increasing length of time a person had had IBD.
This is an observational study, and as such, can't establish cause and effect. Nor were the researchers able to gather information on potentially influential lifestyle factors, such as diet and exercise, or assess the impact of anti-inflammatory drugs prescribed.
But they point to previously published research, indicating chronic inflammation and an imbalance in gut bacteria as potential contributors to cognitive decline.
Their report concludes: "The identification of increased dementia risk and earlier onset among patients with IBD suggest that [they] might benefit from education and increased clinical vigilance [to slow cognitive decline and improve quality of life]".
Obesity and dementia
This study was published on the same day that a study from University College London (UCL) revealed obesity is associated with a 31% increased increased risk of dementia.
Prior evidence has suggested that obesity might cause an increased risk of dementia via its direct influence on cytokines (cell signalling proteins) and hormones derived from fat cells, or indirectly through an adverse effect on vascular risk factors. But the association has remained somewhat unclear due to conflicting findings from different studies.
Therefore researchers conducted a study in which they collected data from 6,582 people in a nationally representative sample of the English population aged 50 years and over, from the English Longitudinal Study of Ageing.
The findings, published in the International Journal of Epidemiology, suggest that people who are obese in late adulthood face a 31% increased risk of dementia than those whose body mass index (BMI) is within the 'normal' range. The study also found the risk may be particularly high for women.
Dr Dorina Cadar, UCL Principal Supervisor and the senior author, said: "These findings provide new evidence that obesity may have important implications in terms of dementia risk.
"Both BMI and waist circumference status should be monitored to avoid metabolic dysregulations. Hence, reducing weight to optimal levels is recommended by adopting healthy and balanced patterns of eating, such as the Mediterranean diet, appropriate physical exercise and reduced alcohol consumption throughout the course of the entire adult life span."
The team found that people whose BMI was 30 or higher (at obese level) at the start of the study period had a 31% greater risk of dementia, at an average follow-up of 11 years, than those with BMIs from 18.5-24.9 (normal level).
There was also a significant gender difference in the risk of dementia associated with obesity. Women with abdominal obesity (based on waist circumference) had a 39% increased risk of dementia compared to those with a normal level. This was independent of their age, education, marital status, smoking behaviour, genetics (APOE ε4 gene), diabetes and hypertension - and yet this association was not found among the male participants.
When BMI and waist circumference were viewed in combination, obese study participants of either gender showed a 28% greater risk of dementia compared to those in the normal range.
Mechanism of effect
The researchers suggest the potential mechanisms by which adiposity contributed to the risk of dementia involved comorbidities, genetics and inflammatory processes. Although some evidence suggests that this association could potentially be mediated by other comorbidities, such as hypertension, cardiovascular diseases and diabetes, the current study did not find evidence to support these notions.
Although APOE-ε4 is a strong genetic risk factor for dementia, the current study found no evidence that APOE-ε4 status has an interaction effect with obesity in this analysis, which is consistent with results from the Finnish CAIDE study.
The precise biological mechanisms of how APOE-ε4 modifies the effects of obesity on the risk of late-life dementia are still poorly understood. It has been suggested that APOE-ε4 triggers inflammatory cascades that lead to neurovascular dysfunction, i.e. blood–brain barrier failure, exposure of toxic derivational proteins from the blood into the brain and decrease of small vessels’ length.
Several endocrine axes bridging the brain and periphery have also been suggested to influence hippocampal and hypothalamic functions by involving adipokines and adipose tissue.
Source: Gut
Zhang B, Wang HE, Bai Y, et al
"Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study"
doi: 10.1136/gutjnl-2020-320789
Source: International Journal of Epidemiology
Yixuan Ma, Olesya Ajnakina, Andrew Steptoe, Dorina Cadar,
"Higher risk of dementia in English older individuals who are overweight or obese"