Effects of Iron Levels and Cerebral Oxygenation on Free and Cued Recall in Elders with Mild Cognitive Impairment
Authors: Wenger Michael J , Carlson Barbara W , De Stefano Lisa A , Butler Kelly K , Curran Kaitlin A , Daji Shaylin K , Mooney Evan H , Herhsey Linda A , Carlson John R 
Published: November 2023

Iron deficiency is known to have negative effects on brain function and cognitive performance during infancy, childhood, and midlife. In later life, these relationships are less well understood. However, factors potentially related to iron status, specifically reductions in cerebral oxygenation during sleep, may also be determinants of cognitive decline. We proposed that low serum iron levels and low cerebral oxygen levels during naps would be related to poor free and cued recall after naps in older adults with amnestic mild cognitive impairment. We report results from an exploratory study of potential relationships between iron status, cerebral oxygenation, and memory in 11 persons (4 men, 58–76 years) with neurologist‐verified amnestic mild cognitive impairment (aMCI), a preclinical state to AD. Memory was assessed using the free and cued selective reminding task (FCSRT), a sensitive measure of aMCI. Thirty‐six images of common items, paired with two cues (a category label and an associated instance) were presented and participants were first asked to recall as many of the items as possible (free recall, FR). Next, 1 or 2 of the cues were presented for a subset of non‐recalled items and participants were asked to recall items given these cues (cued recall, CR). Participants then napped for up to 1 hour and, on awakening, performed FR followed by CR of non‐recalled items. If items remained unremembered, they were studied again, followed by FR and CR; this cycle was repeated until all items were recalled. Testing was done in the afternoon, with participants seated and monitored with EEG and bilateral frontal cerebral oximetry, a measure of mixed venous oxygenation (rcSO2). Of the 11 participants, 2 were iron sufficient (sFt > 20 mg/L), 1 was iron depleted (12 < sFt < 20 mg/L), and 8 were iron deficient (sFt < 12 mg/L); none were anemic (all Hb > 12 g/dL). Participants slept an average of 28.9 m. Mean maximum changes in rcSO2 during naps were −2.5% (right) and −2.9% (left). FR decreased from 12.7 items pre‐nap to 11.7 items post‐nap. CR increased from 7.4 items to 17.3 items. Reaction times during CR were 2736 ms (1 cue) and 2532 ms (2 cues). Higher sFt levels were associated with higher prenap FR (β = 0.010) and lower prenap CR (β = −0.019, both R2 > 0.26). Higher sFt (β = −2.358) and total iron binding capacity (β = −7.894) were associated with shorter CR RT for items with 2 cues (R2 = 0.62). Post‐nap FR was associated with less time asleep (β = −0.271) and higher Hb levels (β = 0.475, R2 = 0.49). Shorter time asleep (β = −0.325) and maximum change in right (β = −0.404) and left (β = −0.339) rcSO2 were associated with smaller pre‐ to post‐nap reductions in FR (R2 > 0.89). We found a set of significant relationships between low serum iron levels (sFt and Hb), cerebral oxygenation changes, and poor free and cued recall before after naps in older adults with amnestic mild cognitive impairment. The consistency of these preliminary findings suggest the need to further examine the potential tradeoffs between iron levels and age‐related changes in cerebral oxygenation.

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Funded by the Vice Presidents for Research, The University of Oklahoma and The University of Oklahoma Health Sciences Center.