Owing to progress in medicine and corollary increases in lifespan, dementia has become a public health concern, thus a primary focus for research. However, cognitive decline is not an inevitable consequence of aging. Studies have shown that while cognitive strategies and response times change with age, the ability to perform tasks successfully remains largely intact. Where significant functional decline is seen, there is a detectable pathological state upon post-mortem analysis. Contrarily, detection of pathology is not indicative of clinical disease, prodromal or de facto.

The term cognitive resilience describes a capacity for the brain to maintain function despite age-related challenges such as neurodegeneration, chronic inflammation, vascular disease, and aberrant protein build-up. Interestingly, healthy aging evinced by cognitive resilience does not mean an individual is devoid of deleterious alleles and aberrant gene expression associated with gross neuropathology; rather, altered mechanisms at molecular, cellular, and biochemical levels derive compensatory profiles that present as cognitive resilience.

Understanding such mechanisms and the molecular underpinnings of cognitive resilience is important for detecting vulnerabilities in aging populations and determining potential therapeutic targets in prodromal states. Of note, much insight comes from studies examining clinical and subclinical states of disease. For example, neurodegeneration-focused brain banks invariably identify cognitively healthy sub-groups despite advanced chronological age at death and postmortem pathology consistent with disease. Investigating these subgroups provides valuable insight into cognitive resilience.

In an effort to define mechanisms of cognitive resilience and show-case innovative developments in the field, this Research Topic will provide an overview of the latest research in molecular and cellular neuroscience by presenting a compilation of studies and reviews utilizing advanced molecular and computational tools in the context of cognitive resilience.

We encourage submissions, including original articles and reviews, across the breadth of molecular and cellular neuroscience related to aging with and without clinical signs or neuropathology, including healthy aging, resilience, and super-ager investigations in human, translational, and cellular models.

Sub-topics of interest include:

- Genomic or DNA-based markers, such as polymorphisms, gene variants, histone and chromatin modifications (or other indications of DNA accessibility for transcriptional machinery), and DNA modifications suggesting mechanistic changes in different aging phenotypes

- Alterations in aberrant protein development and destruction, or lack thereof, in model organisms or cells

- Lifestyle correlations with gene expression, synaptic profiles, protein degradation, vascular health, or indications of aging at the molecular level with and without clinical signs or neuropathology; such as, social engagement, caloric restriction, exercise, reported life-fulfillment, socioeconomic status, and intellectual engagement through hobbies or profession

- Transcriptomic, proteomic, metabolomic studies that demonstrate association with healthy brain aging or senescence in the absence of cognitive or behavioral decline

- Physiological markers and disturbances related to aging as impacting cognitive function and brain mechanistic alterations, for example, blood pressure, body mass, periodontal disease, air and noise pollution, metabolic syndromes, chronic pain, and infectious disease sequelae

- Mechanisms of hormesis, including immediate or delayed response to acute physiological or psychological stressors

- Sleep and circadian rhythm disruptions with advanced chronological age defined by mechanistic changes at the molecular or cellular level

- Biological sex differences in cognitive aging

Are you interested in contributing a manuscript to this Research Topic?

Molecular neuroscience of cognitive resilience