Biopsychosocial Mechanisms of Successful Aging

成功衰老的生物心理社会机制

• 批准号: 10569673
• 负责人: Lisa Feldman Barrett
• 金额: $ 78.86万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10569673
• 关键词: Adult; Affect; Affective; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; American; Amygdaloid structure; Amyloid; Anatomy; Arousal; Autonomic nervous system; Behavior Therapy; Biological; Biological Markers; Brain; Cardiac Output; Cognition; Cognitive; Cognitive aging; Communication; Deterioration; Development; Dimensions; Elderly; Enabling Factors; Exercise; Exhibits; Functional disorder; Funding; Goals; Health; Heterogeneity; Impaired cognition; Impairment; Individual; Individual Differences; Intervention; Intervention Studies; Measures; Memory; Modeling; Motivation; Neurobiology; Outcome; Outcome Measure; Outcomes Research; Participant; Pattern; Performance; Persons; Physiological; Physiological Processes; Population; Public Health; Research; Role; Sampling; Structure; Subgroup; Testing; Vascular resistance; Visceral; age related; behavior measurement; biobehavior; biopsychosocial; body system; cognitive ability; cognitive function; cognitive performance; cognitive task; experience; healthy aging; improved; individual variation; innovation; insight; lifestyle intervention; neural; neural patterning; neuroimaging; neuromechanism; neuropathology; novel strategies; potential biomarker; pre-clinical; predictive marker; preservation; promote resilience; protective factors; psychologic; resilience; response; young adult

It is well-known that in most people, cognitive abilities decline with age. With the elderly population growing (20% of Americans will be over 65 by 2030), this represents a significant public health concern. However, not all older adults show this pattern of decline. We and others have demonstrated that some individuals seem to be resilient to age-related decline, even in the setting of biomarkers of Alzheimer’s disease (AD) neuropathologic changes. Understanding the factors that promote resilience in older adults could point to new approaches to achieve healthy aging in all adults. In our recent studies of aging, we identified substantial heterogeneity within older adults in memory performance and both brain anatomy and connectivity, such that some older participants (60-80 yrs.) were indistinguishable from young adults (18-32). These remarkable individuals offer the opportunity to investigate the biobehavioral mechanisms that contribute to successful aging. Our findings indicated that successful agers (who showed preserved anatomy within and connectivity between multiple limbic and paralimbic structures that subserve motivation, affect, and cognition) exhibited a distinct neural response to challenging tasks when compared to typical agers. Crucially, successful agers also differed in their subjective experience of the task, rating the arousal caused by the task as significantly more pleasant. Together, these results suggest that individual differences in the response to increasing arousal during difficult cognitive tasks contribute meaningfully to cognitive outcomes in aging. Here, we introduce the Arousal along the Challenge/Threat Continuum (ACT-C) model, which hypothesizes that arousal can be helpful or harmful to cognition, depending on how it is expressed in the brain and the body In this proposal, we will test the central hypothesis of the ACT-C model, that individual differences in the experience of affect, and its neurobiological and autonomic physiological correlates predicts cognitive performance in aging. We propose that increased effort and cognitive performance will be associated with a tendency to subjectively experience arousal more as challenge than as threat (Aim 1), an autonomic physiological response to difficult tasks previously associated with a challenge interpretation (i.e. decreased vascular resistance, Aim 2), and a neural ‘challenge’ pattern involving increased mid-cingulate activity and communication between networks (Aim 3). Crucially, we predict that these motivational, physiological, and neural factors will be associated with improved performance even in individuals with evidence of preclinical AD. This research, if successful, will provide much-needed insight into the biological mechanisms by which affect and motivation support cognitive aging. The outcomes of this research could point the way to neural and physiological biomarkers predicting successful aging, which could be used to evaluate interventions to promote successful aging, including in people with biomarker evidence of Preclinical AD.

众所周知，大多数人的认知能力会随着年龄的增长而下降。随着老年人口的增长