Improving the resistance and resilience framework for aging and dementia studies

Abstract

Background: The "resistance vs resilience" to Alzheimer's disease (AD) framework (coping vs avoiding) has gained interest in the field in the last year. In this viewpoint, our effort is (i) to provide clarity to the usage of the framework in the context of the ATN (amyloid/tau/neurodegeneration) system as well as in lifespan and cognitive aging studies and (ii) to discuss the challenges of matching these concepts to specific biological mechanisms. Main body: In the context of the ATN system, the main goal of the resistance vs resilience framework is to make a fundamental distinction between risk factors that may help halt the development of AD pathologies (AT) ("resistance") vs delay processes downstream to AT, i.e., neurodegeneration (N) and the clinical expression of the disease ("resilience"). The process of resilience in dementia and aging research should be envisioned as a process that is developed over the lifespan. Greater neurobiological capital to start with (initial brain reserve), maintaining brain structure and function (brain maintenance), or greater adaptability of cognitive strategies to perform a task (cognitive reserve) could all contribute to higher resilience to pathologies later in life. Simply put, resilience is not only a response to pathological processes (i.e. increased brain function to compensate for increasing AD pathology) but also reflects individual differences in brain structure and function that can be built over the lifespan (e.g., through education, lifetime cognitive, and physical activities). Further, the resistance vs resilience terminology can be extended to study other pathological processes such as cerebrovascular lesions, Lewy body disease, or TDP-43. However, some challenges do exist: (i) when studying multiple neuropathologies, the study design and framework will drive the usage of terminology; (ii) it is unavoidable that the measurements of resilience (brain structure and function) will reflect both the effect of pathologies and the impact of several risk and protective factors throughout the lifespan. Therefore, identifying resilience brain markers across lifespan, aging, and dementia studies, notably with longitudinal study designs, will be an important step towards understanding mechanisms of action.Conclusions: While the field advances towards consensus definitions of existing concepts, the resistance vs resilience terminology may provide clarity in the communication of results in aging and dementia studies as well as provide a framework for the development of both hypotheses and study designs.

Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline

“…Evidence for resistance would be supported by low loads or absence of risk factors, while evidence for resilience would be supported by the exposure to such factors in combination with a higher cognitive performance and/or lower rates of decline. 55 , 56 , 57 …”

“…Resilience may be further explained by the build-up of cognitive reserve. 15 , 56 This concept relates to having more neural resources available by inheritance or lifetime training, allowing higher levels of brain damage to accumulate before clinical symptoms appear. 15 We found that next to physical health factors, factors of cognitive reserve such as education, frequency of cognitive activity, and premorbid IQ were associated with cognitive performance.…”

Sociodemographic, Lifestyle, Physical, and Psychosocial Determinants of Cognitive Reserve

“…has been coined to capture the scientific paradigm that refers to the adaptability that helps to explain differential susceptibility of cognitive abilities or day-to-day function to brain aging, pathology, or insult, and has been described in terms of both resilience and resistance [6]. Indeed, a high cognitive reserve was found to be related to a 47% reduced relative risk of mild cognitive impairment or dementia [7].…”

Measuring Resilience and Resistance in Aging and Alzheimer Disease Using Residual Methods

“…Various heuristic constructs (e.g., cognitive/brain reserve, neural compensation, brain maintenance) have been proposed to describe different aspects of the observed individual differences in brain and cognitive aging trajectories. 1 , 2 Here, we adopt and expand upon a previously proposed framework 3 , 4 that conceptualizes 2 distinct phenomena under the umbrella terms resistance and resilience. Resistance is defined as the brain's ability to avoid age-related senescent and pathologic changes, thereby preserving brain integrity and cognition, despite risk factors such as advanced age or genetic predisposition to Alzheimer disease (AD) pathology.…”

“…Resilience refers to the brain's ability to cope with accumulating senescent and pathologic changes and preserve brain integrity (brain resilience) or cognitive function (cognitive resilience) in the face of significant pathologic burden. 3 , 4 For example, an elderly APOE ε4/ε4 carrier is at increased risk of accumulating AD neuropathology and subsequent cognitive impairment. Remaining relatively free of neuropathology would indicate resistance, while preserving normal cognition despite β-amyloid and tau accumulation indicates (cognitive) resilience.…”