Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Düzel et al., Hippocampus, 2011; 21: 803–814). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE‐SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults' activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age‐group‐related differences for the subsequent memory contrast, and the FADE‐SAME score additionally exhibited age‐group‐related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single‐value scores of memory‐related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.

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Medial temporal lobe dependent cognitive functions are highly vulnerable to hypoxia in the hippocampal region, yet little is known about the relationship between the richness of hippocampal vascular supply and cognition. Hippocampal vascularization patterns have been categorized into a mixed supply from both the posterior cerebral artery and the anterior choroidal artery or a single supply by the posterior cerebral artery only. Hippocampal arteries are small and affected by pathological changes when cerebral small vessel disease is present. We hypothesized, that hippocampal vascularization patterns may be important trait markers for vascular reserve and modulate (i) cognitive performance; (ii) structural hippocampal integrity; and (iii) the effect of cerebral small vessel disease on cognition. Using high-resolution 7 T time-of-flight angiography we manually classified hippocampal vascularization patterns in older adults with and without cerebral small vessel disease in vivo. The presence of a mixed supplied hippocampus was an advantage in several cognitive domains, including verbal list learning and global cognition. A mixed supplied hippocampus also was an advantage for verbal memory performance in cerebral small vessel disease. Voxel-based morphometry showed higher anterior hippocampal grey matter volume in mixed, compared to single supply. We discuss that a mixed hippocampal supply, as opposed to a single one, may increase the reliability of hippocampal blood supply and thereby provide a hippocampal vascular reserve that protects against cognitive impairment.