Cancer diagnoses are associated with better long-term memory in older adults, possibly reflecting a range of social confounders that increase cancer risk but improve memory. We used spouse's memory as a negative control outcome to evaluate this possible confounding, since spouses share social characteristics and environments, and individuals' cancers are unlikely to cause better memory among their spouses. We estimated the association of an individual's incident cancer diagnosis (exposure) with their own (primary outcome) and their spouse's (negative control outcome) memory decline in 3601 couples from 1998 to 2014 in the Health and Retirement Study, using linear mixed-effects models. Incident cancer predicted better long-term memory for the diagnosed individual. We observed no association between an individual's cancer diagnosis and rate of spousal memory decline. This negative control study suggests that the inverse association between incident cancer and rate of memory decline is unlikely to be attributable to social/behavioral factors shared between spouses.
Ospina-Romero M, Brenowitz WD, Glymour MM, Mayeda ER, Graff RE, Witte JS, Ackley SF, Lu KP, Kobayashi LC. (2020). The Association Between Cancer and Spousal Rate of Memory Decline: A Negative Control Study to Evaluate (Unmeasured) Social Confounding of the Cancer-memory Relationship. Alzheimer disease and associated disorders