The Superager Phenotype: What Are the Brain Structure, Lifestyle Characteristics?

Grey matter volume, movement speed, and mental health were significantly associated the superager phenotype.

Both structural brain differences and lifestyle factors are associated with preserved memory function in the superager phenotype, according to study findings published in The Lancet Healthy Longevity. 

Cognitive decline, particularly memory loss, is characteristic of normative aging. However, some individuals known as “superagers” are older adults that demonstrate cognitive function comparable to people decades younger and seem to exhibit resilience to typical age-related memory decline. To characterize the features associated with this phenomenon, researchers conducted a study to assess the brain structure and lifestyle factors of superagers.

The researchers selected study participants from the Vallecas Project, an ongoing, longitudinal cohort study based in Madrid, Spain. The Vallecas Project included participants who were White, aged 70 to 85, independent in activities of daily living, and did not have any diagnosed neurologic or psychiatric disorders at time of enrollment. The study included yearly follow-up visits in which demographic data, neuropsychologic assessments, magnetic resonance imaging (MRI) scans, and blood samples were collected.

The researchers defined superagers as individuals aged 79.5 and older with episodic memory comparable to that of a healthy person aged 20 to 30 years younger, assessed via the Free and Cued Selective Reminding Test. A total of 64 superagers (mean age, 81.9 years; 59% women) and 55 age-matched control individuals with typical aging (mean age, 82.4 years; 64% women) were identified from the cohort.

Our findings illustrate marked differences, both in brain structure and in multiple clinical and lifestyle features, between superagers and a healthy control group with normal memory function for its age range.

Grey matter volume between superagers and adults with typical aging patterns was evaluated over 5 years. Findings from the cross-sectional analysis revealed that compared with typical adults, superagers had greater total grey matter volume.

Using linear mixed modeling, results showed a significant group (coefficient b, -11.9; SE, 4.9; P =.015) and age (coefficient b, -7.5; standard error [SE], 1.1; P <.0001) effect. The researchers also noted a significant group-by-age interaction (coefficient b, -4.1; SE, 1.7; P =.015). Among typical older adults, there was a faster rate of decline in grey matter volume over time (-11.6 cm3 per SD of scaled age; SE, 1.1) compared with superagers (-7.5 cm3 per SD of scaled age; SE, 1.1).

The researchers also used a random forest machine learning approach to analyze the impact of demographic, lifestyle, and clinical factors associated with superageing.

Although there were no differences in overall physical activity between groups, when compared with typical adults, superagers displayed faster motor skills. Participants’ performance on the timed up-and-go test of mobility was significantly correlated with episodic memory performance (r, -0.39; P < .0001). Furthermore, 3 mental health variables were strongly associated with the superager phenotype: anxious state (P =.001), anxious trait (P =.002), and depression (P =.003). On these measures, superagers reported better mental health than typical older adults.

The researchers wrote, “Our findings illustrate marked differences, both in brain structure and in multiple clinical and lifestyle features, between superagers and a healthy control group with normal memory function for its age range.”

Since there were no observed differences in neurodegenerative blood biomarkers between both groups, the researchers concluded, “The observed between-group differences are therefore likely to reflect a superager resistance to age-related memory decline, rather than [2] groups at different points of a dementia-related process.”

Study limitations included an inability to establish causality and a lack of information on social relationships.


Garo-Pascual M, Gaser C, Zhang L, Tohka J, Medina M, Strange BA. Brain structure and phenotypic profile of superagers compared with age-matched older adults: a longitudinal analysis from the Vallecas Project. Lancet Healthy Longev. Published online July 13, 2023. doi:10.1016/S2666-7568(23)00079-X