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000285922 1001_ $$aAbrous, Djoher Nora$$b0
000285922 245__ $$aHallmarks of healthy cognitive aging: inter-individual differences in aging trajectories.
000285922 260__ $$aOxford [u.a.]$$bElsevier$$c2026
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000285922 520__ $$aCognitive aging is a highly heterogeneous process, with some individuals preserving stable cognitive performance across the lifespan while others exhibiting pronounced decline. This marked interindividual variability indicates that chronological age alone is a poor predictor of cognitive health. Rather than reflecting uniform degeneration, cognitive aging emerges from divergent biological trajectories spanning molecular, cellular, and network levels. In this review, we synthesize emerging biological hallmarks of healthy cognitive aging, emphasizing studies that characterize longitudinal cognitive trajectories in humans or distinguish aged individuals who retain learning capacity from those who do not. We focus on the medial temporal lobe, a region critical for episodic memory and spatial navigation, and examine how variability in its integrity contributes to distinct cognitive outcomes. Across species, convergent evidence suggests that cognitive decline is more closely linked to alterations in network regulation and synaptic plasticity than to overt neuronal loss. We identify key mechanisms shaping individual trajectories, including large-scale network organization, excitation-inhibition balance, neuromodulatory tone, glial and vascular regulation, adult hippocampal neurogenesis, and cellular homeostasis. These processes operate within an interconnected system in which disruptions in core regulatory mechanisms can propagate across levels of organization. Together, this synthesis supports a system-level framework in which cognitive resilience depends on the preservation of coordinated network dynamics. We advocate for longitudinal, multidimensional approaches to identify early shifts in regulatory balance and inform strategies to maintain cognitive function across the lifespan.
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000285922 650_7 $$2Other$$aCognitive Aging
000285922 650_7 $$2Other$$aEpisodic Memory
000285922 650_7 $$2Other$$aHallmarks
000285922 650_7 $$2Other$$ainter-individual differences
000285922 650_7 $$2Other$$amedial temporal lobe
000285922 650_7 $$2Other$$aspatial memory
000285922 7001_ $$aBlin, Nicolas$$b1
000285922 7001_ $$aBoraxbekk, Carl-Johan$$b2
000285922 7001_ $$aCatheline, Gwenaelle$$b3
000285922 7001_ $$aFitzsimons, Carlos P$$b4
000285922 7001_ $$aHilscher, Markus$$b5
000285922 7001_ $$aLemoine, Maël$$b6
000285922 7001_ $$aLopes, Luísa V$$b7
000285922 7001_ $$0P:(DE-2719)2811815$$aMaass, Anne$$b8$$udzne
000285922 7001_ $$aNilsson, Mats$$b9
000285922 7001_ $$aNyberg, Lars$$b10
000285922 7001_ $$aRassmussen, Lene Juel$$b11
000285922 7001_ $$aRemondes, Miguel$$b12
000285922 7001_ $$aSauvage, Magdalena$$b13
000285922 7001_ $$0P:(DE-2719)2812631$$aSchreiber, Stefanie$$b14$$udzne
000285922 7001_ $$0P:(DE-2719)2810583$$aWolbers, Thomas$$b15$$eLast author$$udzne
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