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). RELEVANCE (See instructions): 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.
The Clinical Core provides the Projects with data from epidemiological, neuropsychological, medical and physical measures. The Core is responsible for obtaining informed consent for participation in the EAS and for participation in the brain donation program. The Core's primary function is characterization of EAS subjects through baseline and annual follow-up clinical and neuropsychological evaluations, including the assignment of cognitive and dementia diagnoses. All subjects undergo an in-person Clinical Core evaluation at baseline and subsequent 12-month intervals. The Core also conducts Consensus Case Conferences to assign clinical cognitive outcomes for each subject at each Wave (annual evaluation). Clinical outcomes assigned include: 1) Diagnosis of DSM-IV 'Dementia' versus 'No Dementia'; 2) for subjects with dementia, subtypes are diagnoses using standard criteria; and 3) Intermediate States of Cognitive Impairment (amnestic Mild Cognitive Impairment, non-amnestic Mild Cognitive Impairment). The Clinical Core cooperates with the Administrative Core to collect follow-up medical and neuropsychological information for study subjects no longer able to return for in-person evaluations. Data from the Clinical Core are used to determine subject eligibility for participation in Projects. Finally, the Clinical Core collects, distributes, and banks biological specimens for current and future assays. RELEVANCE (See instructions): The Clinical Core collects epidemiological, neuropsychological and neurological data to service research projects. These data are used to assign diagnoses, to develop other outcome variables, correlate with neuropathologic findings and experimental neuropsychological procedures and locomotor outcomes. The Clinical Core ascertains all the confounders and effect modifiers of dementia risk.
