Falls: A Marker of Preclinical AD

Active, not recruiting

• Conditions: Alzheimer Disease; Fall

• Registration Number: NCT04949529
• Lead Sponsor: Washington University School of Medicine

Brief Summary

This longitudinal cohort study investigates cognitively normal participants with and without preclinical Alzheimer disease (AD) in order to examine: (1) the relationship between falls and functional mobility in preclinical stages of AD; and (2) a hypothesized model of central and peripheral mechanism(s) underlying falls and functional mobility in preclinical stages of AD.

Detailed Description

Alzheimer disease (AD) is a slowly progressive neurodegenerative disease. Conversion to symptomatic AD occurs slowly over years through a series of preclinical stages marked by changes in molecular biomarkers. It is unknown whether functional mobility and falls are preclinical markers of AD.

This longitudinal clinical study evaluates a cohort of cognitively normal individuals who are currently undergoing comprehensive clinical, neuropsychological, and biomarker evaluations at the Knight Alzheimer's Disease Research Center (Knight ADRC). They receive an annual in-home evaluation of fall risks and functional mobility and prospective ascertainment of falls. Comparisons of assessments of functional mobility will be performed with regard to measures of brain pathology (i.e., amyloidosis, tau, and neurodegeneration) to allow researchers to characterize when changes in falls and functional mobility occur during preclinical stages of AD.

This study also examines the central and peripheral system mechanism(s) underlying falls and functional mobility in preclinical AD using structural equation modeling.

Study Timeline

• Study Start: 2019-03-07
• Study First Submitted: 2021-04-09
• Study First Submitted QC: 2021-06-25
• Study First Posted: 2021-07-02
• Status Verified: 2024-08
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-04
• Study Completion: 2025-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

1. 65 years of age or older

2. cognitively normal (Clinical Dementia Rating [CDR] score of 0)

   • A pilot sub-study collecting stool will also enroll a few individuals with CDR>0 for comparison.

3. have biomarkers (CSF), and/or neuroimaging (positron emission tomography [PET] and/or magnetic resonance imaging [MRI]) within 2 years of enrolling in this study.

Exclusion Criteria

• History of Parkinson's disease.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change from baseline: Gait Speed	4 years post-enrollment	Gait speed will be collected using the Timed Up and Go (TUG) test.
Change from baseline: Dynamic balance and mobility	4 years post-enrollment	Dynamic balance and mobility will be assessed using the Performance Oriented Mobility Assessment (POMA), a task-oriented assessment.
Number and Severity of Falls	Cumulative falls at 4 years post-enrollment	Prospective monthly fall reporting will be collected using an automated phone/email system. Severity of falls will be calculated using a previously published algorithm.
Change from baseline: Dual-task gait	4 years post-enrollment	Dual-task gait will be collected using the Timed Up and Go Cognitive (TUGcog) and Timed Up and Go Manual (TUGman)

Secondary Outcome Measures

Name	Time	Method
Fall Risk Composite Score	4 years post-enrollment	A fall risk composite score will be calculated using established cut-off values, dichotomized as 0 (no risk), or 1 (fall risk), and summed. Higher score indicate higher fall risk. Constructs that will be included are: vision, alcohol abuse, urinary incontinence, depression, pain, medication, functional capacity with activities of daily living, previous falls, home hazards, and self-efficacy.
Change from baseline: Standing balance and vestibular function	4 years post-enrollment	Center of pressure path will be measured using Balance Tracking System (BTrackS)
Change from baseline: Falls behavior	4 years post-enrollment	Behaviors to prevent falls will be measured using the Falls Behavioral Scale for Older People (FaB)
Change from baseline: Depression	4 years post-enrollment	Frequency of symptoms will be assessed using The Patient Health Questionnaire (PHQ-9) and Geriatric Depression Scale (GDS)
Change from baseline: Sensation	4 years post-enrollment	8-item questionnaire and sensation testing (vibration \[feet\] and sharp \[arms and legs\])
Change from baseline: Lower extremity strength	4 years post-enrollment	Lower extremity strength will be assessed using the 30-Second Chair Stand test and minimal change in the peak torque value
Change from baseline: Grip strength	4 years post-enrollment	Pounds of force will be measured using a handheld dynamometer
Change from baseline: Vision	4 years post-enrollment	Visual acuity will be collected using the Early Treatment Diabetic Retinopathy Study (ETDRS) test, and contrast sensitivity will be measured using the Pelli-Robson test
Change in baseline: Functional performance	4 years post-enrollment	Independence, safety, and adequacy with shopping, checkbook balancing, and medication management will be assessed using the Performance Assessment of Self-Care Skills (PASS)
Change from baseline: Olfaction	2 years post-enrollment	Olfaction will be assessed using the University of Pennsylvania Smell Identification Test (UPSIT)
Change from baseline: Hearing	4 years post-enrollment	Hearing impairment will be assessed using The Hearing Handicap Inventory for the Elderly (HHIE-S)

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States