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Gastrointestinal Biopsy May Determine Risk of Neurodegenerative Disease


People with a gastrointestinal biopsy of normal mucosa or nonspecific inflammation were shown to be at increased risk of Alzheimer disease and Parkinson disease.

A gastrointestinal (GI) biopsy of normal mucosa or nonspecific inflammation may increase risk of Alzheimer disease (AD) and Parkinson disease (PD), according to study findings published in European Journal of Neurology.

AD and PD are neurodegenerative diseases characterized by the progressive and selective loss of neurons in the central nervous system. Previous evidence suggests that GI manifestations may serve as prodromal nonmotor symptoms in neurodegenerative diseases, in which GI symptoms and conditions (eg, inflammatory bowel disease, irritable bowel syndrome) have been linked to the subsequent risk of AD and PD.

“In clinical practice, however, the most frequent histological findings of GI endoscopy are normal histological features, ie, normal mucosa (usually untreated), and inflammatory histological changes not categorized as inflammatory diseases, ie, non-specific inflammation,” explained researchers. “It is therefore interesting and relevant to investigate the subsequent risk of neurodegenerative diseases among individuals with GI symptoms that required a GI endoscopy but with a finding of histologically normal mucosa or nonspecific inflammation.”

They conducted a register-based cohort analysis of the nationwide matched ESPRESSO study, which included information on individuals with any GI histopathological record available from Sweden’s 28 pathology departments during 1965 to 2016, as well as up to 5 individuals per index person who were randomly selected from the Swedish Total Population Register.

Eligible participants included individuals in Sweden with a GI biopsy of normal mucosa (n = 480,346; mean age, 44 years; 62% female patients) or nonspecific inflammation (n = 655,937; mean age, 52 years; 51% female patients) from 1965 to 2016 (exposed group), and their individually matched population references and unexposed full siblings.

Among the study cohort, individuals with normal mucosa tended to have more health care visits, a higher Charlson comorbidity index, and a higher prevalence of previous GI diseases.

During a mean follow-up of 12 years, the incidence rate of AD was 84.10 per 100,000 person-years for individuals with normal mucosa and 78.81 per 100,000 person-years for their matched references. The corresponding numbers were 40.66 vs 36.20 per 100,000 person-years for PD. For individuals with nonspecific inflammation and their matched references, the incidence rate was 129.26 vs 129.76 per 100,000 person-years for AD and 63.64 vs 60.22 per 100,000 person-years for PD.

Findings indicated that those with normal mucosa or nonspecific inflammation had a higher risk of AD and PD during the 20 years after biopsy:

  • Compared with the population references, individuals with normal mucosa had an increased risk of AD (incidence rate [IR] difference: 13.53 per 100,000 person-years; HR, 1.15; 95% CI, 1.11-1.20) and PD (IR difference: 6.72; HR, 1.16; 95% CI, 1.10-1.23)
  • Compared with the population references, individuals with nonspecific inflammation had an elevated risk of AD (IR difference: 13.28; HR, 1.11; 95% CI, 1.08-1.14) and PD (IR difference: 6.83; HR, 1.10; 95% CI, 1.06-1.14)

Similar results were observed in subgroup and sensitivity analyses and when comparing with their unexposed siblings. The lack of information on the indication of GI biopsy was cited as a potential limitation of the study findings. Additionally, due to the different incidence and prevalence of AD and PD across countries, generalization of the findings to other areas should be cautious, noted the researchers.

They concluded that findings add new evidence to the early involvement of GI dysfunction in neurodegenerative disease.


Sun J, Ludvigsson JF, Roelstraete B, et al. Gastrointestinal biopsy of normal mucosa or non-specific inflammation and risk of neurodegenerative disease: nationwide matched cohort study. Eur J Neurol. Published online November 29, 2022. doi:10.1111/ene.15654

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