Felicia W. Sun, Michael R. Stepanovic, Joseph Andreano, Lisa Feldman Barrett, Alexandra Touroutoglou and Bradford C. Dickerson
Journal of Neuroscience 14 September 2016, 36 (37) 9659-9668; DOI: https://doi.org/10.1523/JNEUROSCI.1492-16.2016
Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function.
SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with youthful memory performance) would exhibit preserved neuroanatomy in key brain networks subserving memory. We found that superagers not only perform similarly to young adults on memory testing, they also do not show the typical patterns of brain atrophy in certain regions. These regions are contained largely within two major intrinsic brain networks: the default mode network, implicated in memory encoding, storage, and retrieval, and the salience network, associated with attention and executive processes involved in encoding and retrieval. Preserved neuroanatomical integrity in these networks is associated with better memory performance among older adults.
As humans age, memory and many other cognitive functions often decline. When a neuropsychologist evaluates an older adult, “normal” performance is substantially lower than that of a younger adult. For example, on the California Verbal Learning Test (CVLT), an average 25-year-old remembers 14 words, while an average 75 year-old remembers 9 words, more than 2 SDs lower (Delis et al., 1987). Nevertheless, there is substantial variation in the degree of cognitive decline with age. Some older adults—referred to by one group as “superagers”—continue to perform at a level similar to middle-aged adults (Harrison et al., 2012; Rogalski et al., 2013; Gefen et al., 2014; Gefen et al., 2015), and sometimes even young adults (Weintraub et al., 1994). Investigation of the biological mechanisms associated with “youthful” cognitive function in such individuals is crucial to understanding “successful aging” (Depp and Jeste, 2006). In this study, we sought to replicate and extend prior work on superaging by testing hypotheses regarding the structural integrity of two key brain networks that contribute to memory function.
Memory requires that information be encoded, stored, and retrieved. To explicitly encode information, such as a list of words, an individual must first be motivated to attend to the relevant material, engage working memory, and organize the information (Wolk et al., 2011). Broadly speaking, these functions are subserved by fronto–parietal–cingulate circuitry, variously referred to as attentional (Corbetta and Shulman, 2002), executive (Dosenbach et al., 2006; Cole and Schneider, 2007), working memory (Koechlin et al. 1999; Gruber and Goschke 2004), and/or salience systems (Seeley et al. 2007; Touroutoglou et al., 2012). In conjunction with circuitry supporting semantic memory, this circuitry is engaged when new information is organized within the context of previously existing knowledge (Simons and Spiers, 2003; Squire, 2007). Once encoded, information is consolidated and stored as “long-term episodic memories,” by way of the medial temporal lobe (MTL) memory system localized in the hippocampus, medial temporal cortex, and retrosplenial/posterior cingulate cortex (Squire et al., 2004), as well as other key nodes of the default mode network (Dickerson and Eichenbaum, 2010). When information is subsequently retrieved (e.g., during free recall of a word list), attentional, salience, executive, and semantic networks are engaged in conjunction with the MTL memory system; when any of these brain regions are lesioned, memory retrieval is impaired (Wolk et al., 2011).
Normal aging is well known to be accompanied by widespread reductions in the thickness of many of these brain regions (McGinnis et al., 2011; Bakkour et al., 2013), in parallel with age-related decline in memory function (McDaniel et al., 2008). Age-related atrophy is particularly prominent in key frontoparietal nodes of the working memory, executive, salience, and default mode circuitry, such as in lateral and medial prefrontal and lateral parietal cortices, as well as portions of the cingulate cortex and medial temporal lobe (McGinnis et al., 2011; Bakkour et al., 2013). Based on this summary of the processes that subserve memory function and our knowledge of age-related cortical changes, we hypothesized that superagers would exhibit “youthful” neuroanatomy within the networks summarized here. We further hypothesized that, within the entire group of cognitively normal older adults, the cortical thickness of these brain regions would predict individual differences in memory performance.
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