The Gut - PRO Study

Prior treatment

• Active or previous (within 6 months) participation in an Alzheimer's clinical intervention/trial (can be included if previously enrolled in placebo or control group)
• Known periodic antibiotic use (i.e., prior to dental appointments)
• Oral PS-specific exclusion criteria:
  • Inability (e.g., dysphagia) or unwilling to swallow capsules
  • Active gastrointestinal infection at time of enrollment
  • Known or suspected toxic megacolon and/or known small bowel ileus
  • History of total colectomy or bariatric surgery
  • Concurrent intensive induction chemotherapy, radiation therapy, or biological treatment for active malignancy
  • Unable or unwilling to comply with protocol requirements
  • Expected life expectancy less than 6 months
  • Previous use of probiotic supplementation (PS) or microbiome-based products within 2 months, large doses of commercial probiotics consumed (greater than or equal to 10\^8 cfu or organisms per day). Includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component (ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply). Enrollment after 2 months without probiotic use can be considered for eligibility
  • Patients with severe anaphylactic or anaphylactoid food allergy
  • Solid organ transplant recipients less than or equal to 90 days post-transplant or on active treatment for rejection
  • A condition that would jeopardize the safety or rights of the participant, would make it unlikely for the participant to complete the study, or would confound the results of the study

Other illness

• Standard clinical care for dementia and medications used to treat MCI and Alzheimer's disease are acceptable, including monoclonal antibody therapy
• Significant neurologic disease: Any significant neurologic disease, such as Parkinson's disease, stroke, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, subdural hematoma, multiple sclerosis, seizure disorder, or other significant deficits other than Alzheimer's or Mild Cognitive Impairment
• Alcohol/substance: history of alcohol/substance dependence in the past year.
• Significant medical illness: any significant systemic illness or unstable medical condition occurring during ADRC participation that could affect cognition (other than MCI/AD). Examples include malignant cancer, chemotherapy, HIV, untreated thyroid disease, heart failure, or renal insufficiency
• Current diagnosis with diabetes

Lab values

• Exclusionary factors affecting the microbiome:
  • Previous use of systemic antibiotics (intravenous, intramuscular, or oral) within 3 months (depends on the duration of antibiotic use, i.e., less than 3 months is considered exclusion, however, enrollment after 3 months without antibiotic use can be considered for eligibility)
  • Immune stimulating and/or suppressing medications
  • Immunosuppressed as evaluated by complete blood count (CBC) with differential, which includes white blood cell count, total neutrophil count, and total lymphocyte count
  • Unstable dietary history during the previous month, which is defined as major changes in diet by eliminating or significantly increasing a major food group
  • Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years
  • Major bowel resection at any time
  • Active uncontrolled gastrointestinal disorders or disease including inflammatory bowel disease, ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis; irritable bowel syndrome (moderate-severe); persistent, infectious gastroenteritis, colitis, or gastritis; persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated), or chronic constipation

Other

• Illiterate, blind, or non-English speaking

• MCI/AD or cognitively unimpaired, referred from a Wisconsin clinic that is part of the Wisconsin Alzheimer's Institute's (WAI) network, or recruited from the community. May have participated in:
  • Alzheimer's Disease Research Center (ADRC) clinical core study (2011-0030)
  • ADCP (26695, MCW IRB)
  • Synapse study (2018-1283)
  • ADRC Recruitment Registry (2016-0735)
• At least 60 years of age or older
• Good general health (other than cognitive impairment/dementia) with no conditions/medications affecting the gut microbiome (see exclusion criteria below)
• Willing and able to comply with all study procedures for the duration of the study
• Able to provide signed and dated informed consent form
• Participant is not pregnant, lactating or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile)
• Able to take oral medications
• An informant to answer questionnaires about the participant
  • Additional inclusion criteria for unimpaired participants:
• Has MOCA score that falls within the range defined for cognitively healthy individuals
  • Additional inclusion criteria for participants with MCI/AD
• Abnormal cognitive function documented by neuropsychological testing
• ADRC (2015-0030) Consensus Diagnosis Conference indicates dementia or MCI due to AD (for ADRC, ADCP, and Synapse participants only)
• Meets NIA-AA criteria for MCI or AD.