Aging
Emulating a Target Trial of Flu Shots and Memory Decline Among Older Adults in the United States Yingyan Wu* Yingyan Wu Ryo Ikesu Roch Nianogo Beate R. Ritz Elizabeth Rose Mayeda
Annual flu shots have been suggested to prevent dementia among older adults, but prior studies were limited by short follow-up periods and residual confounding. We used the U.S. representative Health and Retirement Study (1996-2020) to emulate a trial to assess memory decline under a hypothetical flu shot intervention of receiving a flu shot at least once every 4 years over 24 years, compared to the natural course (no specified intervention). Every 4 years, participants self-reported whether they took a flu shot at least once over the prior 2 years. Memory was measured every 4 years using a composite memory score (z-scored to baseline distribution) integrating direct and proxy memory assessments. We used targeted maximum likelihood estimation to simulate memory scores over the study period under the two hypothetical intervention scenarios while addressing time-invariant (baseline age, sex/gender, race/ethnicity, education) and time-varying confounders (marital status, household income, medical insurance, loneliness, chronic disease conditions, depression, and daily functioning). We applied sampling weights, used multi-level multiple imputation to address missing exposure and covariate data, and inverse probability of censoring weights to account for loss to follow-up and death. The analytic sample included 12,362 participants (mean baseline age 59.4 years; 54% women; mean number of flu shots reported during the study period = 3, range 0-7). Average memory decline over 24 years was -1.14 SD units [95% CI: -1.21, -1.07] under the hypothetical flu shot intervention and -1.11 SD units [95% CI: -1.14, -1.07] under the natural course (Figure). Compared to the natural course, the flu shot intervention was not associated with better memory function over follow-up (mean difference at 24 years of follow-up: -0.04 SD units [95% CI: -0.10, 0.03]). Our study suggests flu shots may not prevent memory decline.
