Abstract

Objective: An elevated gamma gap is indicative of high serum concentrations of globulin proteins, some of which elicit acute inflammatory responses. An impaired cognitive function has been linked to central and peripheral inflammation, while exercise is associated with protective, anti-inflammatory benefits. In this study, we evaluated whether the gamma gap is associated with cognitive function among older adults and whether physical activity is favorably associated with cognitive function among those with an elevated gamma gap. Materials and Methods: Data from the 1999–2002 National Health and Nutrition Examination Survey (NHANES) were used to identify 2,352 older adults aged between 60 and 85 years. The gamma gap was evaluated by subtracting albumin from total protein, i.e., gamma gap = total protein (g/dL) – albumin (g/dL). Those at or above 3.1 g/dL (31.0 g/L) were considered to have an elevated gamma gap. The Digit Symbol Substitution Test (DSST) was used to assess cognitive function tasks of pairing and free recall among participants. Participants were asked open-ended questions about participation in leisure-time physical activity over the previous 30 days. Results: Those with an elevated gamma gap (DSST, 44.8) had a lower cognitive function score when compared to those without an elevated gamma gap (DSST, 50.1) (p < 0.001). After adjustments, and among those with an elevated gamma gap, those meeting the moderate-to-vigorous intensity physical activity (MVPA) guidelines (vs. not meeting them) had a DSST score of 6.42 units higher (β = 6.42, 95% CI 3.85–8.99, p < 0.001). Conclusion: In this national sample of older adults, the gamma gap was associated with cognitive function, and among those with an elevated gamma gap, meeting the physical activity guidelines was associated with a higher cognitive function. Relevant clinical implications are discussed, as the gamma gap may be predictive of the risk for early mortality and reduced quality of life. Experimental work is needed to investigate whether physical activity training programs are effective in reducing an elevated gamma gap and preserving optimal cognitive functioning among at-risk individuals.

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