FMT and Alzheimer’s Disease

January 15, 2021

Close your eyes and imagine this: You are in a taxi. The driver asks you for your address and you open your mouth to answer but no words come out. Where do I live again? Embarrassed, you apologize profusely and climb out of the car. Your son would find you soon. Or do I have a daughter? Confused and frustrated, you wander down this unfamiliar street you have walked countless times before, trying to find your way home.

Image credit: the-infinite-opi

What is Alzheimer’s Disease?

Memory loss, poor judgement, increased anxiety… These are the signs of Alzheimer’s disease (AD), a form of dementia which is the leading cause of death in older people. In 2020, 16.8% of Singaporeans were aged 65 and above, with 1 in 10 people aged 60 and above possibly having dementia in 2015. Colloquially dubbed the “Silver Tsunami”, Singapore’s rapidly aging population poses serious economic and social implications. However, there are currently no preventive or disease-modifying treatments for AD.

Thought to be caused by cerebral accumulation of amyloid-beta peptide, most people would pick their brains for a solution to AD (quite literally), but gut feeling might tell one to search elsewhere.

What does the gut microbiome have to do with AD?

In recent years, the gut microbiome has increasingly been associated with the development of neurological diseases such as Parkinson’s disease and multiple sclerosis. As such, it is no surprise that emerging evidence has elucidated alterations in gut microbiome composition in patients with AD, suggesting an involvement of the microbiota-gut-brain axis.

In a study by Hazan (2020), it was found that there was symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile (CDI) infection. To date, this is the first report of a patient who experienced rapid improvement in AD symptoms following FMT for recurrent CDI. The patient had previously failed several courses of antibiotics for CDI, with relapse confirmed via symptom recurrence and positive stool test. Following a gradual 5-year decline in memory and cognition, he was under the care of his primary care physician and his neurologist for the treatment of AD. On his most recent Mini-Mental State Examination (MMSE), the patient scored 20, indicating mild cognitive impairment.

The patient underwent a single FMT infusion using stool from his healthy 85-year-old wife who acted as a donor. The resolution of symptoms occurred in a stepwise manner: At 2 months post-FMT, there was increased mental acuity and improved affect observed with a readministration of the MMSE showing that the patient scored 26, indicating normal cognition. The patient’s CDI symptoms were also resolved, and repeat stool testing 2 months later was negative. By 4 and 6 months post-FMT, there were marked improvements in the patient’s memory and mood, as his MMSE score further increased to 29.

Why is FMT not used as a treatment of AD?

While these findings are groundbreaking, there are gaps in this study that need to be filled. For instance, the AD patient had mild cognitive impairment — would the efficacy of FMT treatment differ with more severe forms of AD? Can FMT be used to treat a patient with only AD, without CDI inflection?

Sequencing of the patient’s microbiome before and after FMT treatment would allow for the comparison of microbiota via DNA analysis. By drawing parallels between MMSE scores and microbiome composition, how different stages of cognitive recovery corresponds with microbiota changes may be observed, thereby establishing a clearer link within the microbiota-gut-brain axis.

As Jeff Goldblum’s iconic scene from “Jurassic Park” goes, “A butterfly can flap its wings in Peking, and in Central Park, you get rain instead of sunshine.” Sure, this anecdote is scientifically inaccurate, but it describes the microbiota-gut-brain axis vividly. The gut is a strange place, teeming with life and mystery. Let us venture into the jungle — not just to survive, but to emerge stronger and healthier than before.

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Hazan S. Rapid improvement in Alzheimer’s disease symptoms following fecal microbiota transplantation: a case report. Journal of International Medical Research. 2020;48(6):030006052092593. doi:10.1177/0300060520925930

About the author

Kathleen Ong is a graduate of ACS (Independent) who is en route to university. She is currently interning at AMILI.