A comprehensive score reflecting memory‐related fMRI activations and deactivations as potential biomarker for neurocognitive aging

Abstract

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.

Single-value scores of memory-related brain activity reflect dissociable neuropsychological and anatomical signatures of neurocognitive aging

“…In previous studies, comprehensive scores reflecting memory-related fMRI activations and deactivations have been constructed as potential biomarkers for neurocognitive aging (FADE and SAME scores) 13, 14 . After this first step towards validation (phase 1: preclinical exploratory studies according to Frisoni et al 6 ), we now aimed to further evaluate the biological and potential clinical relevance of these scores by investigating their relationship with performance in an extensive neuropsychological testing battery as well as brain morphological measures (phase 2: assessing variables associated with biomarkers status 6 ).…”

“…The previously described study cohort 13,20 According to self-report, all participants were right-handed, had fluent German language skills and did not take any medication for neurological or mental disorders. The Mini-International Neuropsychiatric Interview (M.I.N.I.…”

“…As described previously 13 More precisely, let ‫ܬ‬ ା be the set of voxels showing a positive effect in young subjects at an a priori defined significance level (here: p < 0.05, FWE-corrected, extent threshold k = 10 voxels), and let ‫ݐ‬ be the t-value of the ݅-th older subject in the ݆-th voxel on the same contrast. Then, the FADE score of this subject is given by…”

“…Previous studies show that, compared to young individuals, older adults exhibited lower activations of inferior and medial temporal structures and reduced deactivations in the Default Mode Network (DMN) during novelty processing and successful long-term memory encoding 13,16 . To capture age-related deviations from the prototypical fMRI activations in younger participants, we proposed the use of reductionist fMRI-based scores: I.…”

Globally Aging Cortical Spontaneous Activity Revealed by Multiple Metrics and Frequency Bands Using Resting-State Functional MRI

“…Human brain function can be mapped with fMRI during either performing a specific task (i.e., common task-based fMRI, tbfMRI) or resting-state (rsfMRI). Both tbfMRI and rsfMRI can be highly or poorly reliable in characterizing individual differences in brain function (Noble et al, 2019 ; Elliott et al, 2020 ), depending on the metrics of use (Zuo and Xing, 2014 ; Kragel et al, 2021 ; Soch et al, 2021 ). TbfMRI is much better to detect aging or age-related changes associated with a specific cognitive function, although faces significant challenges of developing a single task valid for all different stages of aging, but it is, of course, less suited as a global measure for functional changes.…”