Longitudinal Innate Immunity and Aging Study (LIIA)

Investigating the Contribution of Peripheral Versus Central Nervous System Dysfunction to Cognitive Aging

This study plans to examine biological bases of cognitive aging. The goals of the study are to better understand how immune system markers, measured in the blood and in the spinal fluid, are related to clinical features of aging over time. The study also aims to better understand how different types of biomarkers may relate to immune health and the aging process. This research may ultimately help us better understand what puts individuals at risk for cognitive decline and for Alzheimer's disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy Older Adults Ages 60-89

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy older adults

Description

Inclusion Criteria:

1. Between ages of 60-89
2. Have a reliable study partner who has frequent contact with the subject (i.e., at least twice per month) and is able to provide information about functional abilities
3. Mini Mental State Examination (MMSE) >23
4. Clinical Dementia Rating (CDR) global score of 0
5. No informant report of significant cognitive decline in prior year
6. No evidence from the screening visit suggesting a neurodegenerative disorder (per team neurologist)
7. Willingness to complete both baseline and 2-year follow-up procedures

Exclusion Criteria:

1. Major psychiatric disorder (e.g. schizophrenia, bipolar disorder, untreated major depression within past year)
2. Neurological conditions affecting cognition (e.g. Parkinson's disease, epilepsy (onset prior than 2 years ago), head trauma with loss of consciousness >5 min within past two years, large vessel infarct, mild cognitive impairment, or dementia)
3. CNS immune conditions and other conditions affecting cognition (e.g., multiple sclerosis, paraneoplastic encephalitides; Hashimoto's encephalopathy; systematic lupus erythematosus)
4. Systematic illness (e.g.,current cancer, renal failure, respiratory failure)
5. Substance abuse/dependence (DSM-V criteria)
6. Current medication use likely to affect CNS (e.g., long-acting benzodiazepines, neuroleptics in the phenothiazine and haloperidol families)
7. Current medication use that precludes lumbar punctures (e.g. anticoagulants, antiplatelets, heparin shots, or some other blood thinner medications: Warfarin [coumadin], Pradaxa [dabigatran], Xarelto [rivaroxaban]. Eliquis [apixaban], or Plavix [clopidogrel].
8. Significant sensory or motor deficits that would interfere with cognitive testing
9. Factors that preclude MR imaging (e.g., pacemaker)
10. Factors that preclude lumbar puncture

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of Immune Protein Markers in Blood and CSF	Outcome measures will include longitudinal changes in protein levels of blood inflammation and CSF inflammation	2-Year Changes
Performance on Neuropsychological Measures	Outcome measures will include longitudinal changes in cognitive measures (e.g., memory and executive functions) over time	2-Year Changes
Levels of Exosomal Innate Immune Markers in Blood and CSF	Outcome measures will include longitudinal changes in innate immune markers in exosomes (i.e., extracellular vesicles)	2-Year Changes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Structure	Outcome measures will include baseline structural brain imaging	Baseline
CSF Levels of Alzheimer's Disease Related Markers	Outcome measures will include CSF levels of proteins associated with Alzheimer's disease pathology	2-year change

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2019
• Primary Completion (Estimated): March 31, 2025
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: May 8, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Alzheimer's Disease; COVID-19; Dementia; Older Adult
• Other Study ID Numbers: 18-2607; R01AG058772 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No