Frailty effects on non-demented cognitive trajectories are moderated by sex and Alzheimer’s genetic risk

Abstract

Background: Age-related frailty reflects cumulative multisystem physiological and health decline. Frailty increases the risk of adverse brain and cognitive outcomes, including differential decline and dementia. In a longitudinal sample of non-demented older adults, we examine whether (a) the level and/or change in frailty predicts trajectories across three cognitive domains (memory, speed, and executive function (EF)) and (b) prediction patterns are modified by sex or Alzheimer's genetic risk (Apolipoprotein E (APOE)). Methods: Participants (n = 632; M age = 70.7, range 53-95; 3 waves) were from the Victoria Longitudinal Study. After computing a frailty index, we used latent growth modeling and path analysis to test the frailty effects on level and change in three latent variables of cognition. We tested two potential moderators by stratifying by sex and APOE risk (ε4+, ε4-). Results: First, frailty levels predicted speed and EF performance (level) and differential memory change slopes. Second, change in frailty predicted the rate of decline for both speed and EF. Third, sex moderation analyses showed that females were selectively sensitive to (a) frailty effects on memory change and (b) frailty change effects on speed change. In contrast, the frailty effects on EF change were stronger in males. Fourth, genetic moderation analyses showed that APOE risk (e4+) carriers were selectively sensitive to frailty effects on memory change. Conclusion: In non-demented older adults, increasing frailty is strongly associated with the differential decline in cognitive trajectories. For example, higher (worse) frailty was associated with more rapid memory decline than was lower (better) frailty. These effects, however, are moderated by both genetic risk and sex.

Mild behavioral impairment is related to frailty in cognitively normal older adults: a cross-sectional study

“…Frailty and cognitive impairment are distinguishable facets of aging that interact in the cycle of age-related decline. Our results indicated that in cognitively normal older adults, frailty status was associated with aging-related cognitive declines at-risk for the preclinical phase of cognitive disorders, and consistent with previous studies (7)(8)(9)(10)(11). In their seminal study, Solfrizzi and colleagues reported that frail older adults had a higher prevalence of cognitive impairment than those without frailty (77% vs. 54%) (37).…”

“…Our ndings extend the literature by describing different patterns of associations of MBI and its components with frailty, a pattern not previously established. Prior studies of the link between frailty and cognition have focused on individual functional abilities and assessed only global cognitive ability or limited cognitive domains (9,52). The mechanisms for the association is not clear, but possibly involves abnormalities in biological processes related to aging (53).…”

“…Frailty is increasingly recognized as a fundamental determinant of an individual's vulnerability or resilience to stressors (5) and has been linked to impaired cognition (6). Various neurocognitive disorders including late-life cognitive impairment (7,8), mild cognitive impairment (MCI) (9), dementia(10) and…”

Mild behavioral impairment is related to frailty in non-dementia older adults: a cross-sectional study

“…Frailty may increase the risk of future cognitive decline and that cognitive impairment may increase the risk of frailty suggesting that cognition and frailty may interact in the cycle of age-related decline (54,55). Our results indicated that frailty was associated with aging-related cognitive declines at-risk for the preclinical phase of neurocognitive disorders, and consistent with previous studies (11)(12)(13)(14)(15)(16). In their seminal study, Solfrizzi and colleagues reported that frail older adults had a higher prevalence of cognitive impairment than those without frailty (77% vs. 54%) (56).…”

“…Frailty that combines a range of diverse de cits, is increasingly recognized as a fundamental determinant of an individual's vulnerability or resilience to stressors (9) and has been linked to impaired cognition (10,11). Various neurocognitive disorders, including late-life cognitive impairment(12, 13), mild cognitive impairment (MCI) (14), dementia (15) and Alzheimer's disease (AD) (16,17), have been shown to be associated with frailty. Researchers have also found that frailty and cognitive decline might share common physiological mechanisms, with greater frailty being associated with worse cognition and a faster rate of cognitive decline (18).…”