Introduction: There is a lack of studies examining the link between perceived autonomy and frailty among the oldest old. Therefore, our objective was to fill this gap. Methods: Data were used from the multicenter prospective cohort study “Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+)” (AgeQualiDe; follow-up [FU] wave 9; n = 510 observations in the analytical sample). The average age was 90.3 years (SD: 2.7 years). The Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale (CFS) was used to assess frailty. Socioeconomic and health-related covariates were included in our regression model. The autonomy scale developed by Schwarzer was used to assess perceived autonomy in old age. Results: Adjusting for various confounders, multiple linear regressions showed that lower perceived autonomy was associated with increased levels of frailty (total sample: β = −0.13, p < 0.001; women: β = −0.14, p < 0.001; and men: β = −0.12, p < 0.001). Furthermore, lower perceived autonomy was associated with more depressive symptoms, higher cognitive impairment, and being institutionalized (except for men) in the total sample and in both sexes, but it was not significantly associated with age, sex, marital status, educational level, and social support. Conclusion: Findings indicate that frailty is associated with lower autonomy among the oldest old. More generally, while health-related factors were consistently associated with autonomy, sociodemographic factors (except for being institutionalized) were not associated with autonomy among the oldest old. We should be aware of the strong association between autonomy and physical as well as mental health in very old age.

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