Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important “signal” rather than measurement-related “noise.” Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20–94 years; n = 171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0–2–3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0–2–3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.

Metabolic syndrome (MetS) is a cluster of cardiovascular and metabolic abnormalities that together may increase the risk of developing cognitive decline and dementia; however, the neural substrate is incompletely understood. We investigated cortical thickness in the medial temporal lobe (MTL), hippocampal volume, as well as relationships among metabolic risk factor burden, structure and memory performance. Path-analytic models were tested to explore the relations between MetS risk factor, structure and memory performance. Participants were 65 non-demented, middle-aged and older adults, 34 with and 31 without metabolic syndrome. We analyzed archival T1-weighted magnetic resonance imaging (MRI) acquired at 3T and Total Recall and Delayed Recall scores from the Brief Visuospatial Memory Test Revised (BVMT-R). Middle-aged adults with MetS showed less MTL thickness, particularly in entorhinal cortex; while older adults showed a trend for left hippocampal volume loss. Lower MTL thickness, particularly in entorhinal cortex, was associated with greater metabolic risk factor burden in middle-aged adults. In older adults, hippocampal volume was associated with Total Recall and Delayed Recall, while in middle-age entorhinal cortical thickness mediated the association between metabolic disease burden and episodic memory function. The differential findings in middle-aged and older adults with MetS contribute to an understanding of the relationships between metabolic syndrome, structural changes in the brain and increased risk for cognitive decline.

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Working memory (WM) and its BOLD-related parametric modulation under load decrease with age. Functional connectivity (FC) generally increases with WM load; however, how aging impacts connectivity and whether this is load-dependent, region-dependent, or associated with cognitive performance is unclear. This study examines these questions in 170 healthy adults (Mage = 52.99  19.18) who completed fMRI scanning during an n-back task (0-, 2-, 3-, and 4back). FC was estimated utilizing a modified generalized psychophysiological interaction approach with seeds from fronto-parietal (FP) and default mode (DM) regions that modulated to n-back difficulty. FC analyses focused on both connectivity during WM engagement (task vs control) and connectivity in response to increased WM load (linear slope across conditions).Each analysis utilized within-and between-region FC, predicted by age (linear or quadratic), and its associations with in-and out-of-scanner task performance. Engaging in WM either generally (task vs control) or as a function of difficulty strengthened integration within-and between-FP and DM regions. Notably, these task-sensitive functional connections were robust to the effects of age. Stronger negative FC between FP and DM regions was also associated with better WM performance in an age-dependent manner, occurring selectively in middle-and older-adults.These results suggest that FC is critical for engaging in cognitively demanding tasks, and its lack of sensitivity to healthy aging may provide a means to maintain cognition across the adult lifespan. Thus, this study highlights the contribution of maintenance in brain function to support working memory processing with aging.FC DURING N-BACK ACROSS THE ADULT LIFESPAN 6 Impact StatementThe literature examining functional connectivity (FC) during working memory (WM) in healthy adults is mixed in both age effects and its relationship to performance. This study contributes to the literature by examining a large, adult lifespan sample, increased levels of WM load, and additional investigation of connections within and between fronto-parietal and default mode regions. Results revealed age-invariant strengthened FC during WM, suggesting that healthy aging may be resilient to FC changes. Additionally, negative FC between regions was associated with better WM performance in middle-aged and older adults, highlighting the important of FC maintenance to support successful WM ability.FC DURING N-BACK ACROSS THE ADULT LIFESPAN