Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853
Performing Department
Human Development
Non Technical Summary
The cognitive changes associated with healthy aging can alter our quality of life and impact our communities as aging individuals lose independence, require care from family members or paid practitioners, and are less able to contribute to community activities. The proportion of aged New Yorkers has been increasing steadily, and is expected to pose a mounting financial strain (source: NY Office for the Aging). This proposal will establish a basis for simple and effective tools that directly target the biological mechanisms of cognitive aging to combat age-related changes in cognition. These proposed techniques will capitalize on the influences of body state on the brain and cognition. Although it's long been observed that physical health correlates with preserved cognition in older adults, this has amounted to little more than general recommendations of exercise. Exercise, of course, becomes less of an option as our physical abilities decrease with age. Conversely, commercial brain training programs are often too limited in their cognitive improvements, and costly.The proposed interventions will emphasize simple brain-body techniques, like deep breathing, that may be readily learned and easily distributed to seniors in rural areas, provide more general cognitive improvements, and be applied by older adults with limited physical ability. By elucidating how to tailor interventions to improve body-brain connectivity that can influence cognition, this proposal will lay the foundation for effective and lasting tools for cognitive protection during aging. Government funding is imperative to bring this non-commercial alternative to fruition.
Animal Health Component
60%
Research Effort Categories
Basic
30%
Applied
60%
Developmental
10%
Goals / Objectives
By elucidating how specific connections between the body and the brain may be targeted to revitalize the neurochemical systems underlying cognitive performance, this proposal will address critical gaps in current interventions and establish a foundation for developing effective and noninvasive tools to ameliorate the cognitive decline associated with healthy aging. With an estimated 2.6 million New Yorkers over the age of 65 (source: NY Office for the Aging), the availability of simple non-invasive, easy, and cost-free body-brain techniques that successfully protect widespread cognitive functions are crucial to the state's economic and social vitality. Such interventions will help our older adults maintain independent living and hopefully reduce the emotional and financial load for caregivers and costs for paid care. Providing our older adults with tools to sustain cognitive function will grant a sustained quality of life and the ability to remain actively engaged in work and community life.A key theme of this proposal is to ensure that our empirical research and tool development match the needs of the targeted users. Accordingly, one goal is to understand and characterize what seniors need and desire of an intervention, and to integrate this information into our research trajectory. A second goal is to develop a mechanistic understanding of how the body impacts brain activity to regulate cognitive functions, knowledge that is crucial to develop tools that are focused on these biological systems and thus are maximally effective and efficient for seniors. Gaining this biological insight from human participants is intractable, so it is necessary to adopt a model organism. Rats are an excellent model for this type of work because they both have very similar physiology to humans and are capable of learning the same cognitive tasks used in many human experiments. Thus, our final goal is to apply basic research on body-brain connections and their role in cognitive aging in this rodent model to application in humans interventions.ObjectivesGoal: understand and characterize what seniors need and desire of an interventionObjective 1: Conduct semi-structured in-person interviews with seniors in the community to investigate how interventions against cognitive decline can be tailored to meet older adults' needs.Objective 2: Delineate a relationship between vagal activity in the body (measured by heart rate variability), acetylcholine-based cognitive tasks, and performance on a range of cognitive functions in healthy seniors. Delineate a relationship between vagal activity (measured by heart rate variability), acetylcholine activity in the brain, and cognition in a healthy aging rodent model.Goal: develop a mechanistic understanding of how the body impacts brain activity to regulate cognitive functionsObjective 1: Delineate a relationship between vagal activity (measured by heart rate variability) and acetylcholine activity in the brain in a healthy aging rodent model.Delineate a relationship between vagal activity (measured by heart rate variability), acetylcholine activity in the brain, and cognition in a healthy aging rodent model.Objective 2: Manipulate VNS parameters to examine whether directly altering this body-brain pathway will mitigate observed age-related cognitive changes in a healthy aging rodent model.Goal: apply basic research on body-brain connections and their role in cognitive aging in rats to application in humans interventions.Objective 1: Confirm, in healthy aging humans, that non-invasive VNS assessed in the rodent model will translate and exert similar cognitive benefits.
Project Methods
EffortsAt the core of brain-body communication is the vagus nerve, a nerve that connects the autonomic nervous system (body) to the central nervous system (brain) and that uses the neurochemical acetylcholine to communicate between both components. Critically, declining acetylcholine function in the brain underlies features of cognitive aging. It has been shown that vagal nerve stimulation (VNS) is a successful therapy for numerous conditions, but VNS has not yet been applied to interventions against cognitive decline. Hence our overarching research objective is to establish how non-invasive and simple methods for VNS may be used to increase acetylcholine function and enhance cognition in older adults.Year 1: We will bring older adults (>60 years) into the lab and travel out to the community to conduct semi-structured interviews with these seniors, to gain an in-depth qualitative understanding of this population's attitudes towards cognitive decline and how interventions against cognitive decline can be tailored to meet older adults' needs.In a simultaneous rodent experiment, we will make direct recordings of acetylcholine in the brain via electrochemical electrodes and heart rate variability (HRV), the primary metric of vagal integrity in young (approximately 6 months) and aged (approximately 20 months, out of an average 24-month natural lifespan) rats. We will examine the dynamics of HRV and acetylcholine release to investigate age-related differences in these relationships.Year 2: Young (18-30 years) and older (>60 years) adult human participants will complete an established task of cognitive flexibility, a central element of cognitive function that declines with age. Our laboratory has used both human and rodent versions of this task successfully in the past, and this task is known to rely on acetylcholine functioning. As participants complete the task, pulse data will be collected, and subsequently in-house analysis scripts will be applied to extract heart rate variability information from pulse recordings. Participants will also complete the NIH Toolbox ® Cognition Battery to assess performance on a broad range of cognitive functions, and four screens for dementia and cognitive decline. Our analysis will probe the relationship between heart rate variability, performance on the cognitive flexibility task, overall cognitive functioning as measured by the Cognition Battery, and cognitive decline as measured by the screening tools.We will then train rats to complete the same cognitive flexibility task employed in human participants. This odor discrimination version of the task replicates that used previously by Dr. De Rosa. As rats perform this task we will collect electrochemical recordings of acetylcholine release and heart rate variability data as described in Year 1. We will examine the dynamics of HRV and acetylcholine release that correlate with successful and unsuccessful cognitive task performance in both aged (approximately 20 months) and young (approximately 6 months) rats to investigate age-related differences in these relationships. We will specifically probe whether differences in HRV patterns across the lifespan can explain differences in acetylcholine release and whether these in turn can explain differences in cognition.Year 3: Using direct electrical VNS via an implanted stimulator, we will tailor VNS parameters to address observed differences in vagal and acetylcholine activity associated with cognitive aging. For example, if it is found that individual baseline HRV is most predictive of acetylcholine activity and cognitive abilities, then chronic VNS to induce persistent changes may be most applicable, whereas an observation that short bursts of vagal activity during a task underlie differences would suggest that acute VNS, when needed, may be most impactful.Using the electrochemical electrodes and cognitive flexibility task described above, quantities and dynamics of acetylcholine release in the brain and cognitive task performance will be measured in young and aged rats with and without VNS. We hypothesize that optimally tailored VNS will improve aged rats' performance relative to young rats.Having established the specific VNS parameters required to attenuate age-related changes to acetylcholine activity in rats, we will apply these findings to human experiments. Young (18-30 years) and aged (>60 years) adults will perform a replication of the cognitive experiment from Year 2. However, rather than only recording vagal activity via heart rate variability, we will now non-invasively manipulate vagal activity based on our findings from rodent experiments, and measure the impact of this manipulation on cognitive performance. The vagus nerve can be stimulates non-invasively through controlled breathing and through rubbing the outer ear. We hypothesize that in the absence of VNS, older adults will show a performance deficit compared to young adults and that targeted VNS will improve cognitive flexibility in older adults to provide reliable gains relative to that of young adults.EvaluationWe will take measures throughout the project to ensure progress toward our expected community outcomes as well. Through our engagement efforts we will solicit input from older adults in the community throughout the project. During year 1 we will use surveys and interviews with older adults to ensure that our research moves toward tools that will be adopted by this community. We will specifically address what qualities older adults seek in non-invasive interventions, what approaches to cognitive protection will they choose to use and their reasons for these choices, and what format (i.e. written material, live presentation) older adults will find most useful for conveying cognitive protection techniques. In year 3, we will share advice based on our research findings, which we will develop into informational resources. We will use surveys before and after receipt of these resources to measure whether the body-brain tools are engaging and applicable to older adults and whether any subjective or objective cognitive improvement is detected, and will revise future resources accordingly.