Emerging Liver Brain Axis in Neurodegeneration*

Date/Time: Sunday, September 10, 2023 - 11:45 AM – 12:45 PM
Track: Interactive Lunch Workshop
Room: Franklin Hall 2 (4th Floor)
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Session Evaluation Form: https://myana.org/form/ana2023-session-evaluation-emerg

Chair: James Gugger, MD, PharmD

Co-Chair: Neal Parikh, MD, MS, RPNI

This session would provide an in-depth overview of data supporting the epidemiology and mechanisms that pertain to the emerging recognition that liver-related factors and liver disease contribute to neurodegenerative disease, cognitive impairment, dementia, and brain aging. It is now well accepted that isolated neurodegeneration is the exception and not the rule. In other words, many people with cognitive impairment and dementia have multiple contributory factors. While vascular disease and vascular risk factors have received much attention, there is growing recognition of the contribution of systemic factors. The number of publications on the impact of liver disease and related conditions on cognitive impairment and dementia has dramatically increased in the past 5 years. Advances in this area include multiple, complementary epidemiological analyses demonstrating a compelling link between liver disease and cognitive impairment/dementia, mechanistic work pertaining to standard Alzheimer’s disease biomarkers, and provocative work regarding liver-derived factors and neurogenesis. A forum to discuss these advances will foster creative collaboration across disciplines and may clarify research priorities in this area.

Learning Objectives:

  • Describe the changing epidemiology of chronic liver diseases.
  • Recognize the impact of clinical and subclinical liver disease on cognitive impairment and dementia.
  • Understand at least three potential mechanisms by which liver-related factors may impact cognitive brain health.

The Liver-Brain Axis: An Epidemiological Perspective on Cognitive Impairment and Dementia

Speaker: Neal Parikh, MD, MS, RPNI

Chronic liver diseases are highly prevalent conditions. The impact of chronic liver diseases on other organ systems is well appreciated. There is growing recognition that chronic liver diseases may impact cognitive brain health, dementia risk, and neurodegeneration. This presentation will overview the changing epidemiology of chronic liver diseases from the vantage point of neurology, and will also overview epidemiological data establishing a link of chronic liver diseases with cognitive impairment and dementia. 

Systemic mechanisms of exercise induced brain rejuvenation 

Speaker: Saul Villeda, PhD

Aging drives cognitive impairments in the adult brain. It is imperative to gain insight into what drives aging phenotypes in the brain in order to maintain, and even restore, functional integrity in the elderly. We, and others, have shown that systemic manipulations - such as heterochronic parabiosis (in which a young and old circulatory system are joined) and administration of young blood plasma - can reverse age-related impairments in regenerative and synaptic processes, as well as rescue cognitive faculties in the aged brain. More recently, my lab demonstrated that administration of liver-derived exercise induced blood factors can likewise partially reverse age-related loss of plasticity in the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged brain as a means to rejuvenate regenerative, synaptic and cognitive functions late in life. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating pro-youthful and pro-aging effects of blood-borne factors. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting exercise induced rejuvenation in the aging brain.

Insights From ADNI: Altered Bile Acid Profiles and AD Markers

Speaker: Kwangsik Nho, PhD

Bile acids (BA) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Mounting evidence suggests gut microbiota influence pathological features of Alzheimer’s disease (AD) (“gut-liver-brain axis”). However, it is unclear how peripheral changes in BA profiles can influence central changes in AD such as amyloid-β and tau burden. Our lab has investigated if serum BA levels would be associated with biomarkers for AD pathophysiology including neuroimaging (MRI and PET) and cerebrospinal fluid (CSF) based on the emergent NIA-Alzheimer’s Association Research Framework (A/T/N) for AD to show serum-based BA metabolites are associated with “A/T/N” biomarkers for AD. Results provide further support that BA signaling machinery is likely implicated in AD.

Insights from the Framingham Study: NAFLD, Liver Fibrosis, and Neurodegeneration

Speaker: Galit Weinstein, PhD 

Besides the well-established link between advanced forms of liver disease and poor cognitive function, recent evidence suggests that the presence of even pre-cirrhotic stages of chronic liver disease may be related to an elevated risk of cognitive impairment. Particularly, non-alcoholic fatty liver disease may be related to cognitive decline and dementia risk. The presentation will include an overview of findings from the Framingham Heart Study cohorts on the link between non-alcoholic fatty liver disease and markers of Alzheimer's disease. In addition, plausible mechanisms and future research directions will be discussed.