Converging lines of evidence from anatomical, clinical, and experimental studies from Einstein Aging Study and other aging cohorts indicate that the locomotor function is impaired early in the course of cognitive decline, and may be a marker for cognitive and non-cognitive outcomes in older adults. We conceptualize locomotor function in older adults as those performed under simple and complex conditions. Simple locomotor functions are defined as walking at normal pace without any distractions, and are measured using clinical rating scales and quantitative methods. Complex locomotor functions are those required to maintain locomotion in presence of cognitive (walking while talking) and environmental (spatial navigation) challenges. The complex condition may more closely approximate 'real world'abilities, and by stressing locomotor function in high-risk adults reveal early stages of cognitive and locomotor decline. Our overall hypothesis is that cognition and locomotion functions are vulnerable to common disease processes that result in impairments, which in turn will help identify individuals at high risk for cognitive and motor decline. While multiple pathological pathways lead to cognitive and locomotor decline, in this Einstein Aging Study program project 3 (Locomotor Function In Cognitive Aging And Cognitive Decline) we will focus on vascular status and function as well as hippocampal function and morphology that are vulnerable to processes such as stress and pain. Building on our studies during our current funding period that have established locomotion-cognition associations in the Einstein Aging Study cohort, we propose a comprehensive study of locomotion and cognition in almost 1300 participants (active and to be recruited) over a five-year period with the following aims. We will establish the role of subclinical vascular pathology and brain substrates assessed using multiple neuroimaging modalities on locomotion (Aim 1). We will examine the influence of hippocampal morphology and function, measured using neuroimaging and memory functions, on locomotion (Aim 2). Explore the temporal relationships of locomotion and cognition in aging (Aim 3). Finally, we will define the role of simple and complex locomotion tasks in predicting cognitive transitions and falls in older adults in community and institutional settings (Aim 4).

Public Health Relevance

Project 3 aims to determine the role of locomotor function in cognitive aging and cognitive decline. Establishing the role of simple and complex locomotor deficits in different stages of cognitive decline will have a major impact on enhancing strategies of very early detection of cognitive decline, with important implications for treatment of related outcomes.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-1)
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Albert Einstein College of Medicine
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Graff-Radford, Jonathan; Lesnick, Timothy G; Boeve, Bradley F et al. (2016) Predicting Survival in Dementia With Lewy Bodies With Hippocampal Volumetry. Mov Disord 31:989-94
Strauss, S B; Kim, N; Branch, C A et al. (2016) Bidirectional Changes in Anisotropy Are Associated with Outcomes in Mild Traumatic Brain Injury. AJNR Am J Neuroradiol :
Callisaya, Michele L; Ayers, Emmeline; Barzilai, Nir et al. (2016) Motoric Cognitive Risk Syndrome and Falls Risk: A Multi-Center Study. J Alzheimers Dis 53:1043-52
Allen, Mariet; Carrasquillo, Minerva M; Funk, Cory et al. (2016) Human whole genome genotype and transcriptome data for Alzheimer's and other neurodegenerative diseases. Sci Data 3:160089
Williams, Kelly L; Topp, Simon; Yang, Shu et al. (2016) CCNF mutations in amyotrophic lateral sclerosis and frontotemporal dementia. Nat Commun 7:11253
Ezzati, Ali; Katz, Mindy J; Zammit, Andrea R et al. (2016) Differential association of left and right hippocampal volumes with verbal episodic and spatial memory in older adults. Neuropsychologia 93:380-385
Ezzati, Ali; Katz, Mindy J; Lipton, Michael L et al. (2016) Hippocampal volume and cingulum bundle fractional anisotropy are independently associated with verbal memory in older adults. Brain Imaging Behav 10:652-9
Carrasquillo, Minerva M; Barber, Imelda; Lincoln, Sarah J et al. (2016) Evaluating pathogenic dementia variants in posterior cortical atrophy. Neurobiol Aging 37:38-44
Zammit, Andrea R; Katz, Mindy J; Derby, Carol et al. (2016) Metabolic Syndrome and Smoking Are Associated with Future Development of Advanced Chronic Kidney Disease in Older Adults. Cardiorenal Med 6:108-15
Walton, Ronald L; Soto-Ortolaza, Alexandra I; Murray, Melissa E et al. (2016) TREM2 p.R47H substitution is not associated with dementia with Lewy bodies. Neurol Genet 2:e85

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