TY  - JOUR
AU  - Abrous, Djoher Nora
AU  - Blin, Nicolas
AU  - Boraxbekk, Carl-Johan
AU  - Catheline, Gwenaelle
AU  - Fitzsimons, Carlos P
AU  - Hilscher, Markus
AU  - Lemoine, Maël
AU  - Lopes, Luísa V
AU  - Maass, Anne
AU  - Nilsson, Mats
AU  - Nyberg, Lars
AU  - Rassmussen, Lene Juel
AU  - Remondes, Miguel
AU  - Sauvage, Magdalena
AU  - Schreiber, Stefanie
AU  - Wolbers, Thomas
TI  - Hallmarks of healthy cognitive aging: inter-individual differences in aging trajectories.
JO  - Ageing research reviews
VL  - Advance online publication
SN  - 1568-1637
CY  - Oxford [u.a.]
PB  - Elsevier
M1  - DZNE-2026-00368
SP  - 103102
PY  - 2026
AB  - Cognitive aging is a highly heterogeneous process, with some individuals preserving stable cognitive performance across the lifespan while others exhibiting pronounced decline. This marked interindividual variability indicates that chronological age alone is a poor predictor of cognitive health. Rather than reflecting uniform degeneration, cognitive aging emerges from divergent biological trajectories spanning molecular, cellular, and network levels. In this review, we synthesize emerging biological hallmarks of healthy cognitive aging, emphasizing studies that characterize longitudinal cognitive trajectories in humans or distinguish aged individuals who retain learning capacity from those who do not. We focus on the medial temporal lobe, a region critical for episodic memory and spatial navigation, and examine how variability in its integrity contributes to distinct cognitive outcomes. Across species, convergent evidence suggests that cognitive decline is more closely linked to alterations in network regulation and synaptic plasticity than to overt neuronal loss. We identify key mechanisms shaping individual trajectories, including large-scale network organization, excitation-inhibition balance, neuromodulatory tone, glial and vascular regulation, adult hippocampal neurogenesis, and cellular homeostasis. These processes operate within an interconnected system in which disruptions in core regulatory mechanisms can propagate across levels of organization. Together, this synthesis supports a system-level framework in which cognitive resilience depends on the preservation of coordinated network dynamics. We advocate for longitudinal, multidimensional approaches to identify early shifts in regulatory balance and inform strategies to maintain cognitive function across the lifespan.
KW  - Cognitive Aging (Other)
KW  - Episodic Memory (Other)
KW  - Hallmarks (Other)
KW  - inter-individual differences (Other)
KW  - medial temporal lobe (Other)
KW  - spatial memory (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41865894
DO  - DOI:10.1016/j.arr.2026.103102
UR  - https://pub.dzne.de/record/285922
ER  -