Age-related reduction of BOLD modulation to cognitive difficulty predicts poorer task accuracy and poorer fluid reasoning ability

Abstract

Aging is associated with reduced resources needed to perform difficult cognitive tasks, but the neural underpinnings are not well understood, especially as there is scant evidence linking functional brain differences to aging cognition. Therefore, the current study examined modulation of fMRI activation from easier to harder spatial distance judgments across a large lifespan sample (N=161; ages 20–94) to identify when in the lifespan modulation to difficulty begins to show deficits and if age-related modulation predicts cognition. Analyses revealed two sets of regions in which modulation increased with difficulty due to either more activation (positive modulation) or more deactivation (negative modulation) to difficulty. These two networks evidenced differential aging trajectories: a right-lateralized fronto-parietal network that decreased in modulation to difficulty between middle- and older-age, and a network of regions in ventromedial prefrontal cortex, posterior cingulate, left angular and middle frontal gyri that showed decreased modulation at the transition from younger to middle-age. Critically, older adults who maintained negative modulation to difficulty showed higher task accuracy. Further, individuals who showed greater coupling between positive and negative modulation performed better on a fluid reasoning task. Age-related preservation of coupled modulation in both cognitive control regions and regions typically associated with default network may be a salient marker of how the brain adapts to maintain cognitive function as we age.

Structure and function of the aging brain

“…We have recently shown that increased coupling of these networks, as predicted by the DECHA is associated with reduced fluid intelligence and increased reliance on semantic or crystalized knowledge in older adulthood [126]. Recent evidence both from cross-sectional [96] and longitudinal [127] investigations provide support for this hypothesis and provide further evidence that these changes in network interactivity can predict individual differences in cognitive functioning. Taken together these network-based accounts of functional brain aging point to network neuroscience as an important new frontier in neurocognitive aging research.…”

“…Finally, substitution reflects activation of entirely novel neural networks in older relative to younger adults, perhaps signaling strategy differences or functional reorganization [e.g. 96,97].…”

“…Age-related changes include reduced suppression [112,116,117] and decreased within-network connectivity during both task [110,113,118] and rest [108,109,119,120]. Recent evidence also suggests that the default network is more functionally connected to other brain networks in aging [113,114,[119][120][121][122] and this connectivity is poorly modulated by task context [96,97,[122][123][124].…”

Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance

“…Structural changes in APOE protein impact its ability to bind with lipids and ␤-amyloid and to reduce its functional ability to maintain neuronal health (Frieden and Garai, 2012;Liu et al, 2013). Indeed, 4-positive (4ϩ) individuals are more likely to accumulate extracellular ␤-amyloid (A␤) protein, as the APOE4 isoform reduces A␤ clearance and increases A␤ aggregation (Verghese et al, 2011).…”

“…Indeed, 4-positive (4ϩ) individuals are more likely to accumulate extracellular ␤-amyloid (A␤) protein, as the APOE4 isoform reduces A␤ clearance and increases A␤ aggregation (Verghese et al, 2011). Without adequate clearance, ␤-amyloid can form oligomers and plaque, which are thought to be neuro-toxic to neurons (Liu et al, 2013;Scheltens et al, 2016). Thus, APOE4 carriers are likely to show reduced efficiency in neural function, and fMRI evidence suggests that differences in taskrelated brain function are apparent in even younger adults Dennis et al, 2010;Matura et al, 2014;Suri et al, 2015), far preceding the development of AD.…”