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@ARTICLE{Abrous:285922,
      author       = {Abrous, Djoher Nora and Blin, Nicolas and Boraxbekk,
                      Carl-Johan and Catheline, Gwenaelle and Fitzsimons, Carlos P
                      and Hilscher, Markus and Lemoine, Maël and Lopes, Luísa V
                      and Maass, Anne and Nilsson, Mats and Nyberg, Lars and
                      Rassmussen, Lene Juel and Remondes, Miguel and Sauvage,
                      Magdalena and Schreiber, Stefanie and Wolbers, Thomas},
      title        = {{H}allmarks of healthy cognitive aging: inter-individual
                      differences in aging trajectories.},
      journal      = {Ageing research reviews},
      volume       = {Advance online publication},
      issn         = {1568-1637},
      address      = {Oxford [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2026-00368},
      pages        = {103102},
      year         = {2026},
      abstract     = {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.},
      subtyp        = {Review Article},
      keywords     = {Cognitive Aging (Other) / Episodic Memory (Other) /
                      Hallmarks (Other) / inter-individual differences (Other) /
                      medial temporal lobe (Other) / spatial memory (Other)},
      cin          = {AG Wolbers / AG Maaß},
      ddc          = {610},
      cid          = {I:(DE-2719)1310002 / I:(DE-2719)1311001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41865894},
      doi          = {10.1016/j.arr.2026.103102},
      url          = {https://pub.dzne.de/record/285922},
}