A Traitlike Dimension of Subjective Memory Concern Over 30 Years Among Adult Male Twins

Abstract

ImportanceSubjective memory concern has long been considered a state-related indicator of impending cognitive decline or dementia. The possibility that subjective memory concern may itself be a heritable trait is largely ignored, yet such an association would substantially confound its use in clinical or research settings.ObjectiveTo assess the heritability and traitlike dimensions of subjective memory concern and its clinical correlates.Design, Setting, and ParticipantsThis longitudinal twin cohort study was conducted from 1967 to 2019 among male adults with a mean (SD) age of 37.75 (2.52) years to follow-up at mean ages of 56.15 (2.72), 61.50 (2.43), and 67.35 (2.57) years (hereafter, 38, 56, 62, and 67 years, respectively) in the Vietnam Era Twin Study of Aging. The study included a national community-dwelling sample with health, education, and lifestyle characteristics comparable to a general sample of US men in this age cohort. Participants were monozygotic and dizygotic twins randomly recruited from the Vietnam Era Twin Registry. Data were analyzed from May 2021 to December 2022.Main Outcomes and MeasuresMeasures included subjective memory concern at 4 time points; objective memory, depressive symptoms, and anxiety at the last 3 time points; negative emotionality (trait neuroticism) at age 56 years; polygenic risk scores (PRSs) for neuroticism, depression, and Alzheimer disease; APOE genotype; and parental history of dementia. Primary outcomes were heritability and correlations between subjective memory concern and other measures.ResultsThe sample included 1555 male adults examined at age 38 years, 520 at age 56 years (due to late introduction of subjective memory concern questions), 1199 at age 62 years, and 1192 at age 67 years. Phenotypically, subjective memory concerns were relatively stable over time. At age 56 years, subjective memory concern had larger correlations with depressive symptoms (r, 0.32; 95% CI, 0.21 to 0.42), anxiety (r, 0.36; 95% CI, 0.18 to 0.51), and neuroticism (r, 0.34; 95% CI, 0.26 to 0.41) than with objective memory (r, −0.24; 95% CI, −0.33 to −0.13). Phenotypic results were similar at ages 62 and 67 years. A best-fitting autoregressive twin model indicated that genetic influences on subjective memory concern accumulated and persisted over time (h2 = 0.26-0.34 from age 38-67 years). At age 56 years, genetic influences for subjective memory concern were moderately correlated with genetic influences for anxiety (r, 0.36; 95% CI, 0.18 to 0.51), negative emotionality (r, 0.51; 95% CI, 0.44-0.57), and depressive symptoms (r, 0.20; 95% CI, 0.10 to 0.29) as well as objective memory (r, −0.22; 95% CI, −0.30 to −0.14). Similar genetic correlations were seen at ages 62 and 67 years. The neuroticism PRS was associated with subjective memory concern at age 38 years (r, 0.10; 95% CI, 0.03. to 0.18) and age 67 years (r, 0.09; 95% CI, 0.01 to 0.16). Subjective memory concern was not associated with any Alzheimer disease risk measures.Conclusions and RelevanceThis cohort study found stable genetic influences underlying subjective memory concern dating back to age 38 years. Subjective memory concern had larger correlations with affect-related measures than with memory-related measures. Improving the utility of subjective memory concern as an indicator of impending cognitive decline and dementia may depend on isolating its statelike component from its traitlike component.

Subjective Cognitive Decline and Genetic Propensity for Dementia beyond Apolipoprotein ε4: A Systematic Review

“…In particular, a longitudinal study conducted by Selwood et al [ 43 ] included 338 monozygotic and 274 dizygotic twin pairs without dementia, revealing that SMC were low to moderately heritable, as just one third (33%) of the SMC variance was explained by genetic factors, while environmental factors were responsible for 67% of the SMC variance. Similar results were obtained by Bell et al [ 44 ] who did not find an association between SMC and parental FH of AD in 1.555 twin male individuals studied prospectively, showing that the heritability for SMC ranged from 26% to 34% in males aged 38–67. Last but not least, Caracciolo et al [ 45 ] assessed 11.926 twin individuals from the large Swedish cohort study for SMC via a telephone interview, concluding that SMC occurrence was not related to genetic background.…”

“…In total, eight family studies were included [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], either relating FH of AD to SCD (five studies) or examining SCD heritability in twin individuals (three studies). Family studies are shown in Table 1 .…”

“…Data regarding the association of polygenic risk for AD and SCD are very limited as only three relevant studies have been published [ 44 , 49 , 50 ], shown in Table 3 .…”

“…However, increased neuroticism PRS was associated with SMC (OR: 1.10, p = 0.007). The same PRS for AD was also used in the aforementioned twin study conducted by Bell et al [ 44 ], in which it was not associated with SMC in a statistically significant manner.…”

“…All twin studies [ 43 , 44 , 45 ] concluded that there was no association between SCD and genetic background. However, questions arise regarding the generalizability of these results in different populations, as the ethnic background of participants was limited, and all studies included community-dwelling populations, while one study included only male individuals [ 44 ].…”