A 25 -year study of “Superages” reveals the brain and lifestyle factors that help certain older adults challenge the typical memory decline, offering clues to stimulate cognitive resilience through lifespan.
Participants in the Northwestern University Superaging Study met on May 24, 2013 to mix and socialize. Photograph by Ben Kesling, at the time with the Wall Street Journal. Study: the first 25 years of the University of the North-West University program
In a recent article published in the journal Alzheimer’s and dementiaResearchers from the Northwestern University Alzheimer’s Disease Research Center (ADRC) have studied “Superage ”, a specific organic and cognitive phenotype and defined on the operational level in people over 80 years of age who perform and individuals who are 20 to 30 years younger on memory tests.
The Superages, they found, show the cellular characteristics and the brain structures which resist the typical decreases associated with age, in particular reduced inflammation, distinct models of “resistance” to the development of pathology and “resilience” with its cognitive impact, and to higher densities of certain specialized neurons.
The term “superagement” (no space between “super” and “ger”) was deliberately chosen as symbolic designation for this quantitative threshold rather than a generic description.
Background
The human brain changes over time through constructive and regressive processes. At the start of life, adaptive changes dominate, but with age, these are gradually undermined by biological factors.
Neurons are particularly vulnerable because they do not regenerate, work intensely to transmit information and consume large amounts of energy, leading to cumulative wear. Aging is often linked to the narrowing of the brain, the loss of neurons and synapses and the accumulation of harmful proteins, which has reinforced the opinion that the cognitive decline is inevitable.
Historically, the prospects for aging ranged from pessimism to a belief in the lasting value of judgment and wisdom. Modern neurosciences have largely highlighted negative opinion, in particular due to research on Alzheimer’s disease showing that most elderly develop brain changes related to this condition.
The University of the North-West University program started in the mid-1990s after an unusual autopsy of an 81-year-old woman with exceptional memory and a pathology linked to minimum Alzheimer’s disease.
This discovery suggested that a significant memory loss is not inevitable and has inspired a research program to identify biological traits that protect certain elderly people against cognitive decline.
About the study
The researchers have defined the Superages as individuals aged 80 and over who marked at least 9 out of 15 on the auditory Rey of the verbal learning test (RAVLT), corresponding to the average performance from 56 to 66 years old, but well above the typical score for their age of 5 out of 15.
The candidates also had to operate at least at an age suitable for age on other cognitive tests. Episodic memory has been chosen as the main criterion because it is the area most affected by aging.
Participants were recruited from cognitively normal checks in the northwest clinical nucleus of the ADRC and via references, although only 10% of the references met the area criteria.
The study finally registered 290 participants, including 101 suckers and 32 neurotypical peers, with an average age of approximately 90 years. The gift of the brain was encouraged, which resulted in 77 autopsies.
Researchers also collected data on social commitment, lifestyle and personality. Although the Superages did not have healthier medical profiles or do not follow “healthy” lifestyles, they tended to be very sociable, to report positive relationships and to mark more in extraversion. Researchers have also noted that these characteristics of the personality align with the role of the anterior cingular cortex in social and emotional treatment, one of the regions of the brain preserved in the Superages.
Longitudinal monitoring has evaluated neuropathology, brain imaging and cognitive stability. The neuroimperie has concentrated on the cortical thickness, in particular in the anterior cingular. Neuropathological analysis has examined the density of neurons, protein accumulations, integrity of the cholinergic system and microglial activity.
Key conclusions
Neuroimagery has shown that, unlike typical elderly people, the superages had no cortical slimming compared to much younger adults, and thinning occurred more slowly over time.
Surprisingly, their anterior cingular cortex was thicker than in 50 to 60 years and contained more neurons von Economic, which are specialized cells linked to social and emotional treatment. The authors note that the superages can be born with a higher density of these neurons, as this does not seem to decrease with age in neurotypical adults.
Post mortem studies have revealed fewer neurofibrillar tangles linked to Alzheimer’s disease in critical regions of memory such as Entorhinal Cortex and Hippocampus. The authors highlighted two possible mechanisms: resistance to the development of these tangles and resilience to their cognitive effects. In some cases, the size of the neurons in the Entorhinal layer two was greater, perhaps conferring resistance or resilience to age-related changes. The SuperiSters also had lower blood rates of phosphorylated Tau, in particular the P-TU181, supporting a reduced pathology.
The cholinergic system of the basal anterior brain, important for attention and memory, has shown less tangles and axonal anomalies in superages, as well as a lower density of neurons rich in acetylcholinesterase – potentially increasing the effect of acetylcholine by reducing its degradation.
Microglial activation in the white substance has also been reduced, suggesting a lower inflammatory load. Preliminary work has also revealed that the microglia of superger brains has unique characteristics and different models of culture proliferation.
A detailed case study has shown remarkable cognitive stability over 15 years, minimal brain atrophy, normal hippocampal and amygdal volumes and sparse pathology without amyloid deposits or other age -related brain diseases.
These results suggest that supervision involves both structural preservation and biological resistance to current neurodegenerative processes, supporting exceptional memory performance well in advanced age.
Conclusions
The Northwestern University Superie program has shown that it is possible to identify individuals in the 1980s and beyond who retains the performance of memory comparable to these younger decades and who have a distinctive neurobiological profile.
This clinicobiological phenotype, characterized by a preserved cerebral morphology, a density of larger economy neurons, robust cholinergic systems, reduced neurofibrillary degeneration and lower inflammation of the white substance, offers a precious contrast to understand the mechanisms stimulating the typical cognitive decline.
A key force is the integration by the program of clinical, neuroimperie and post mortem longitudinal data, allowing a robust characterization of the phenotype. The results suggest that the Superie reflects a relative domination of constructive neuroplasticity compared to involutional processes, potentially modulated by genetic, epigenetic and environmental factors. Candidates genes such as Klotho, Bdnf, Apoe, REPOSet TMEM106B have been proposed as possible contributors, although their role in supervision remains to be determined.
The limitations include the small proportion of the population meeting the supervision criteria and uncertainty as to whether the protective features are innate or modifiable. The authors also warn that conventional neuropathological stadification systems, such as Braak stages, can underestimate the preserved neurons which contribute to the function maintained in the Superages.
Future research should clarify causal mechanisms, assess interventions to delay changes in regressive brain and explore pharmacological pathways to improve resilience and resistance, potentially benefiting from cognitive longevity in the aging population.