Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial

Abstract

Background: Maintenance of cognitive abilities is of critical importance to older adults, yet few effective strategies to slow cognitive decline currently exist. Multivitamin supplementation is used to promote general health; it is unclear whether it favorably affects cognition in older age.

Objectives: To examine the effect of daily multivitamin/multimineral supplementation on memory in older adults.

Methods: The COcoa Supplement and Multivitamin Outcomes Study Web (COSMOS-Web) ancillary study (NCT04582617) included 3562 older adults. Participants were randomly assigned to a daily multivitamin supplement (Centrum Silver) or placebo and evaluated annually with an Internet-based battery of neuropsychological tests for 3 y. The prespecified primary outcome measure was change in episodic memory, operationally defined as immediate recall performance on the ModRey test, after 1 y of intervention. Secondary outcome measures included changes in episodic memory over 3 y of follow-up and changes in performance on neuropsychological tasks of novel object recognition and executive function over 3 y.

Results: Compared with placebo, participants randomly assigned to multivitamin supplementation had significantly better ModRey immediate recall at 1 y, the primary endpoint (t(5889) = 2.25, P = 0.025), as well as across the 3 y of follow-up on average (t(5889) = 2.54, P = 0.011). Multivitamin supplementation had no significant effects on secondary outcomes. Based on cross-sectional analysis of the association between age and performance on the ModRey, we estimated that the effect of the multivitamin intervention improved memory performance above placebo by the equivalent of 3.1 y of age-related memory change.

Conclusions: Daily multivitamin supplementation, compared with placebo, improves memory in older adults. Multivitamin supplementation holds promise as a safe and accessible approach to maintaining cognitive health in older age. This trial was registered at clinicaltrials.gov as NCT04582617.

Keywords: aging; clinical trial; cognition; diet; multivitamins; remote testing.

FIGURE 1

The COSMOS study and its ancillary studies. COSMOS, COcoa Supplement and Multivitamin Outcomes Study.

FIGURE 2

Schematic depiction of the COSMOS-Web Tasks: 1) ModRey list learning task: Participants were presented with a list of 20 words, one at a time, for 3 s each, with the instruction to try to remember the words. Recall was assessed, by having participants type in all the words they remembered, immediately after the word list was presented, and again after ∼15-min delay, following administration of the other tests in the battery. To account for the possibility of typographical errors, responses with ≥80% match to the letters in the original word were scored as correct, unless they spelled out a different common English word. For example, for “river,” “riber” would be counted as correct, but “rider” would not. 2) ModBent object recognition task: Participants first complete 20 matching trials where they are shown a stimulus and are asked to pick it out from an array of two stimuli. Then participants complete 40 forced-choice recognition trials where they indicate if a given stimulus had been studied in the matching trials, and 3) Flanker task: Participants are shown an array of colored arrows, and asked to indicate the color of the central arrow as a test of executive control. Trials vary on directional congruency (that is, whether the direction of the arrow matches the correct response) and color congruency (that is, whether the surrounding arrows are the same color as the central arrow). COSMOS, COcoa Supplement and Multivitamin Outcomes Study.

FIGURE 3

CONSORT diagram. ITT, intention-to-treat.

FIGURE 4

Mean improvement on ModRey immediate recall between treatment groups. Error bars represent 95% CIs.