JMIR Publications

ABSTRACT

Background:

Gait dysfunction is a preclinical marker of Alzheimer's disease (AD) and related dementias (ADRD), often emerging years before clinical diagnosis. While much of the existing literature has focused on the pathological mechanisms driving motor and cognitive decline, the neural and biological substrates that confer resilience against such decline remain poorly understood. Individuals who maintain exceptional gait performance into advanced age termed Super Movers represent a unique phenotype of resilient aging. Understanding the biological profile of these individuals offers a unique and largely untapped window into the mechanisms underlying healthy aging and resilience to dementia.Gait dysfunction is a preclinical marker of Alzheimer's disease (AD) and related dementias (ADRD), often emerging years before clinical diagnosis. While much of the existing literature has focused on the pathological mechanisms driving motor and cognitive decline, the neural and biological substrates that confer resilience against such decline remain poorly understood. Individuals who maintain exceptional gait performance into advanced age termed Super Movers represent a unique phenotype of resilient aging. Understanding the biological profile of these individuals offers a unique and largely untapped window into the mechanisms underlying healthy aging and resilience to dementia.

Objective:

This study aims to identify the structural, functional, neurophysiological, and molecular brain characteristics that distinguish exceptionally mobile older adults from their usual and slow-moving peers, and to determine whether these characteristics predict cognitive and physical decline over time. We hypothesize that the interplay between protective and pathological mechanisms in aging gives rise to structural, functional, neurophysiological, and molecular brain changes that manifest along a continuum from resilient gait to gait dysfunction.

Methods:

We aim to enroll 350 adults aged 65 years and older from community and clinic settings. Participants will be classified by gait speed into fast, usual, and slow movers using age- and sex-specific thresholds; fast movers aged 80 and older will be designated as Super Movers. All participants will undergo comprehensive assessments at baseline including brain imaging, mobile EEG recorded during walking, multisensory integration, comprehensive blood profiling, blood-based markers of neurodegeneration, epigenetic and proteomic aging clocks, and detailed cognitive testing. Follow-up assessments will be conducted annually in person and every six months by telephone.

Results:

This study was funded by the National Institute on Aging (R01AG089096; PI: Joe Verghese) and has received Institutional Review Board approval from Stony Brook University. Enrollment is currently underway.

Conclusions:

Fast and Super Movers are expected to demonstrate distinct neural substrates, EEG activation signatures, and favorable biomarker profiles relative to usual and slow movers. By shifting the scientific focus from the biology of gait decline toward the biology of gait resilience, this protocol is uniquely positioned to advance our understanding of healthy aging and inform novel strategies for dementia prevention.