285922 20260408133425.0 10.1016/j.arr.2026.103102 doi pmid:41865894 pmid 1568-1637 ISSN 1872-9649 ISSN DZNE-2026-00368 English 610 Abrous, Djoher Nora 0 Hallmarks of healthy cognitive aging: inter-individual differences in aging trajectories. Oxford [u.a.] 2026 Elsevier article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1775647963_22723 PUB:(DE-HGF) Review Article ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Cognitive Aging Other Episodic Memory Other Hallmarks Other inter-individual differences Other medial temporal lobe Other spatial memory Other Blin, Nicolas 1 Boraxbekk, Carl-Johan 2 Catheline, Gwenaelle 3 Fitzsimons, Carlos P 4 Hilscher, Markus 5 Lemoine, Maël 6 Lopes, Luísa V 7 Maass, Anne P:(DE-2719)2811815 8 dzne Nilsson, Mats 9 Nyberg, Lars 10 Rassmussen, Lene Juel 11 Remondes, Miguel 12 Sauvage, Magdalena 13 Schreiber, Stefanie P:(DE-2719)2812631 14 dzne Wolbers, Thomas P:(DE-2719)2810583 15 Last author dzne 10.1016/j.arr.2026.103102 p. 103102 - PERI:(DE-600)2099320-1 103102 Ageing research reviews Advance online publication 2026 1568-1637 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)2811815 External Institute I:(DE-HGF)0 Extern 14 P:(DE-2719)2812631 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 15 P:(DE-2719)2810583 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 Nationallizenz StatID:(DE-HGF)0420 StatID 2024-12-21 ger DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-21 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-21 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-21 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2024-12-21 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-21 DBCoverage StatID:(DE-HGF)1120 StatID BIOSIS Reviews Reports And Meetings 2024-12-21 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-21 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-21 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2024-12-21 Peer Review StatID:(DE-HGF)0030 StatID ASC 2024-12-21 I:(DE-2719)1310002 AG Wolbers Aging, Cognition and Technology 0 I:(DE-2719)1311001 AG Maaß Multimodal Neuroimaging 1 journal EDITORS VDBINPRINT I:(DE-2719)1310002 I:(DE-2719)1311001 UNRESTRICTED