# Dynamic neurocognitive adaptation: childhood and adult-midlife engagement associated with later-life brain structure and cognition in older adults with and without mild cognitive impairment

**Authors:** Filippo Cieri, Jessica Z. K. Caldwell, Dietmar Cordes, Chad L. Cross

PMC · DOI: 10.1007/s11682-026-01122-0 · 2026-03-21

## TL;DR

The study shows that childhood and midlife activities like cognitive, physical, and creative engagement are linked to better brain structure and cognition in older adults, even those with mild cognitive impairment.

## Contribution

The study introduces the dynamic Neurocognitive Adaptation (dNA) framework as a multidimensional, time-resolved model of resilience in aging.

## Key findings

- Childhood cognitive engagement is associated with stronger semantic fluency and larger brain volumes in cingulate and temporal regions.
- Midlife engagement correlates with thicker orbitofrontal cortex and larger lingual volumes in later life.
- No mediation or moderation by sex, education, or diagnosis was observed in the associations between engagement and brain outcomes.

## Abstract

Resilience in aging—the capacity to maintain cognition and function despite neuropathology—has been described through cognitive reserve, brain reserve, and maintenance. The dynamic Neurocognitive Adaptation (dNA) framework expands these constructs by defining resilience as a lifelong process of adaptive engagement across cognitive, physical, creative, and social domains that shape neural integrity and cognitive outcomes over time.

Fifty-eight older adults (39 cognitively normal, 19 with mild cognitive impairment) completed neuropsychological testing, amyloid assessment, and structural MRI. The dNA scale quantified engagement across seven life-course time windows. Hierarchical multiple regressions examined domain- and time-specific associations between dNA scores and cortical thickness or regional volumes (FreeSurfer 7.3.2), controlling for age, sex, education, and diagnosis. Exploratory mediation and moderation models tested indirect and interaction effects of demographic and diagnostic factors.

Childhood (Time Window 1) emerged as a sensitive period: higher cognitive engagement is associated with stronger semantic fluency, and physical engagement is linked to a better episodic learning. Creative and physical engagement during childhood related to larger anterior and posterior cingulate and temporal-pole volumes. In adulthood and midlife (Time Windows 3–5), greater engagement was associated with thicker right lateral orbitofrontal cortex and larger lingual volumes. No mediation or moderation by sex, education, or diagnosis was observed.

Childhood and midlife emerge as sensitive periods linking multidomain engagement with later-life brain structure and cognition. The dNA framework provides a multidimensional, time-resolved model of resilience, illustrating how lifelong adaptive behaviors support neural integrity and cognitive health across aging and Alzheimer’s-disease risk.

The online version contains supplementary material available at 10.1007/s11682-026-01122-0.

## Linked entities

- **Diseases:** Alzheimer’s-disease (MONDO:0004975)

## Full-text entities

- **Genes:** COG5 (component of oligomeric golgi complex 5) [NCBI Gene 10466] {aka CDG2I, GOLTC1, GTC90}, COG1 (component of oligomeric golgi complex 1) [NCBI Gene 9382] {aka CDG2G, LDLB}, COG4 (component of oligomeric golgi complex 4) [NCBI Gene 25839] {aka CDG2J, COD1, SWILS}
- **Diseases:** AD (MESH:D000544), amyloid (MESH:C000718787), Dementia (MESH:D003704), functional impairment in instrumental activities of daily living (MESH:D020773), Cognitive Aging (MESH:D003072), psychiatric (MESH:D001523), Neurodegenerative Disease (MESH:D019636), MCI (MESH:D060825), PCC (OMIM:115700), Aging and (MESH:D019588)
- **Chemicals:** AG071566 (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13004746/full.md

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Source: https://tomesphere.com/paper/PMC13004746