Abstract
IMPORTANCE: Subjective memory complaints (SMCs) are associated with a faster cognitive decline; whether this association is also associated with structural brain alterations, such as white matter hyperintensity (WMH) volumes, requires investigation. OBJECTIVE: To evaluate the association of SMCs with WMH volumes and cognitive decline and investigate the role of WMH volumes in the association between SMCs and cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: The Chicago Health and Aging Project, a population-based cohort study, enrolled adults aged 65 years or older. Data collection occurred in 3-year cycles from 1993 until 2012. Our study comprised 975 participants with magnetic resonance imaging assessments, of which 900 participants had data on SMCs and covariates, and 713 participants provided 2 or more cognitive assessments during the follow-up. Statistical analyses were conducted from May to October 2021. EXPOSURES: SMCs were obtained from self-reported questionnaire data during clinical evaluations, and the cycle, when reported, constituted the baseline of our study. Based on the frequency and severity of concerns, we categorized participants into 3 groups, (1) no concerns, (2) moderate concerns, and (3) very worried. MAIN OUTCOMES AND MEASURES: Volumetric magnetic resonance imaging measures of WMH volume and neuropsychological testing assessments of global cognition. Linear regression analysis was used to investigate the association between SMCs and WMH volumes in a multivariable model adjusted for age, sex, race and ethnicity, education, APOE4 status, and total intracranial volume. The association of SMCs with cognitive decline was investigated using linear mixed-effects models for age, sex, race and ethnicity, education, APOE4 status, follow-up time, and each variable in interaction with time to estimate the annual longitudinal change in cognitive function. RESULTS: Of the 900 participants with data on SMCs, covariates, and WMH volumes, 553 (61.4%) were women, 539 (59.9%) were African American, and the mean (SD) age was 79.5 (6.2) years. SMCs were associated with a larger WMH volume and faster cognitive decline. Compared with participants with no concerns, participants who were very worried had higher WMH volumes (β = 0.833; 95% CI, 0.203-1.463) and 174% faster cognitive decline (β = -0.049; 95% CI, -0.076 to -0.022). The association between SMCs and cognitive decline remained statistically significant among individuals with large WMH volumes (ie, within the fourth quartile). Within the fourth quartile of WMH volumes, participants who were very worried had 428% faster cognitive decline (β = -0.077; 95% CI, -0.144 to -0.011) compared with participants with no concerns. CONCLUSIONS AND RELEVANCE: This cohort study suggests that SMCs, frequently reported by older individuals, are an important sign of cognitive impairment, especially among people with abnormalities in brain structure, such as larger WMH volumes.