8-Year Changes in Frailty in Adults: Links to Cognitive and Physical Function and Mortality

Abstract Deficit accumulation frailty indices are being evaluated as clinical markers of biological aging. In this context, it is to be expected that changes over time in such indices should be predictive of downstream changes in cognition, physical function, and mortality. We derived a frailty index (FI) based on deficit accumulation in 38 functional, behavioral, and clinical characteristics and examined associations between 8-year changes in FI and subsequent standardized measures of cognitive and physical function and mortality collected over years 8-18. We drew data from the Look AHEAD clinical trial of a multidomain intensive lifestyle intervention (ILI) in 3841 adults, aged 45-76 years at baseline with overweight/obesity and type 2 diabetes mellitus. Greater FI increases tended to occur among individuals who were older, non-Hispanic White, heavier, and who had greater baseline multimorbidity. Greater increases in FI were associated with subsequently worse levels of composite cognitive function and 400m walk speed (all p<0.001). Additionally, compared with the lowest tertile of FI change, hazard ratios [95% confidence intervals] for 10-year mortality for the middle and highest tertiles of FI change were 1.28 [1.03.1.58] and 1.56 [1.24,1.96], respectively. While assignment to ILI was associated with smaller 8-year increases in FI, this did not translate overall to better cognitive functioning compared to the Diabetes Support and Education control condition across years 8-18. Increase in FI over 8 years predicts subsequent reduced function and greater mortality. However, whether interventions generally targeting FI reduce risks for downstream outcomes remains to be seen.

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Eight Year Changes in Multimorbidity and Frailty in Adults with Type 2 Diabetes Mellitus: Associations with Cognitive and Physical Function and Mortality

The Journals of Gerontology Series A ◽

10.1093/gerona/glab342 ◽

2021 ◽

Author(s):

Mark A Espeland ◽

Jamie Nicole Justice ◽

Judy Bahnson ◽

Joni K Evans ◽

Medha Munshi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Physical Function ◽

Frailty Index ◽

Biological Aging ◽

Older Individuals ◽

Deficit Accumulation ◽

Increased Risk

Abstract Background Indices of multimorbidity and deficit accumulation (i.e. frailty indices) have been proposed as markers of biological aging. If true, changes in these indices over time should predict downstream changes in cognition and physical function, and mortality. Methods We examined associations that 8-year changes in 1) a multimorbidity index comprised of nine chronic diseases and 2) a frailty index (FI) based on deficit accumulation in functional, behavioral, and clinical characteristics had with subsequent measures of cognitive and physical function over 10 years. We drew data from 3841 participants in the Look AHEAD clinical trial. They were aged 45-76 years at baseline and at risk for accelerated biological aging due to overweight/obesity and type 2 diabetes mellitus. Results 1501 (39%) of the cohort had 8-year increases of one among the nine diseases tracked in the multimorbidity index and 868 (23%) had increases of >2. Those with greatest increases in multimorbidity tended to be older individuals, males, and non-Hispanic whites. Greater FI increases tended to occur among individuals who were older, non-Hispanic white, heavier, and who had more baseline morbidities. Changes in multimorbidity and FI were moderately correlated (r=0.26; p<0.001). Increases in both multimorbidity and FI were associated with subsequently poorer composite cognitive function and 400m walk speed and increased risk for death (all p<0.001). Conclusions Accelerated biological aging, as captured by multimorbidity and frailty indices, predicts subsequent reduced function and mortality. Whether intensive lifestyle interventions generally targeting multimorbidity and FI reduce risks for downstream outcomes remains to be seen.

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IMPACT OF AN INTENSIVE MULTIDOMAIN LIFESTYLE INTERVENTION ON DEFICIT ACCUMULATION FRAILTY INDICES

Innovation in Aging ◽

10.1093/geroni/igz038.2874 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S781-S781

Author(s):

Felicia Simpson ◽

Nicholas M Pajewski ◽

Alain M Bertoni ◽

Frank Ingram ◽

Barbara M Nicklas ◽

...

Keyword(s):

Type 2 Diabetes ◽

Lifestyle Intervention ◽

Frailty Index ◽

Biological Aging ◽

Controlled Clinical Trial ◽

Deficit Accumulation ◽

Dietary Counseling ◽

Two Indices ◽

Over Time

Abstract Background: Type 2 diabetes and obesity increase accumulation of health deficits over time and may accelerate biological aging. It is unknown whether multidomain lifestyle interventions can mitigate against this. Methods: Within a large, randomized controlled clinical trial of intensive lifestyle intervention (ILI) including caloric restriction, increased physical activity, dietary counseling, and risk factor monitoring compared with diabetes support and education (DSE) we examined the trajectory of frailty across 8 years. We used two complementary frailty index (FI) definitions, one modeled on work in the Systolic Blood Pressure Intervention Trial; the other including additional deficits related to aging with obesity and type 2 diabetes mellitus. Differences between intervention groups and the consistency of these across clinical subgroups were assessed with re-randomization tests. Results: Data from 4859 adults (45-76 years at baseline, 59% female) were analyzed. Random assignment to ILI was associated with lower FI scores throughout 8 years of follow-up (p<0.001), over which time mean differences between intervention groups averaged 5.8% and 5.4% for the two indices. At year 8, the percentages of participants categorized as frail (FI>0.21) were lower among ILI (39.8% and 54.5%) compared with DSE (42.7% and 60.9%) for the two indices (both p<0.001). Intervention benefits were relatively greater for individuals who were older, not obese, and without history of cardiovascular disease at baseline. Conclusions: Eight years of multidomain lifestyle intervention slows the accumulation of health deficits over time in overweight or obese adults with type 2 diabetes.

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Physical Function Following a Long-Term Lifestyle Intervention Among Middle Aged and Older Adults With Type 2 Diabetes: The Look AHEAD Study

The Journals of Gerontology Series A ◽

10.1093/gerona/glx204 ◽

2017 ◽

Vol 73 (11) ◽

pp. 1552-1559 ◽

Cited By ~ 13

Author(s):

Denise K Houston ◽

Rebecca H Neiberg ◽

Michael E Miller ◽

James O Hill ◽

John M Jakicic ◽

...

Keyword(s):

Type 2 Diabetes ◽

Older Adults ◽

Physical Function ◽

Lifestyle Intervention ◽

Middle Aged ◽

Look Ahead ◽

The Look

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Functional Aging Index Complements Frailty in Prediction of Entry Into Care and Mortality

The Journals of Gerontology Series A ◽

10.1093/gerona/glz155 ◽

2019 ◽

Vol 74 (12) ◽

pp. 1980-1986 ◽

Cited By ~ 2

Author(s):

Deborah Finkel ◽

Ola Sternäng ◽

Juulia Jylhävä ◽

Ge Bai ◽

Nancy L Pedersen

Keyword(s):

Predictive Value ◽

Cox Regression ◽

Frailty Index ◽

Rate Of Change ◽

Chronological Age ◽

Biological Aging ◽

Growth Curve Models ◽

Aging Index ◽

Hazard Ratios

Abstract Background The aim of this study was to develop a functional aging index (FAI) that taps four body systems: sensory (vision and hearing), pulmonary, strength (grip strength), and movement (gait speed) and to test the predictive value of FAI for entry into care and mortality. Method Growth curve models and Cox regression models were applied to data from 1,695 individuals from three Swedish longitudinal studies of aging. Participants were aged 45–93 at intake and data from up to eight follow-up waves were available. Results The rate of change in FAI was twice as fast after age 75 as before, women demonstrated higher mean FAI, but no sex differences in rates of change with chronological age were identified. FAI predicted entry into care and mortality, even when chronological age and a frailty index were included in the models. Hazard ratios indicated that FAI was a more important predictor of entry into care for men than women, whereas it was a stronger predictor of mortality for men than women. Conclusions Measures of biological aging and functional aging differ in their predictive value for entry into care and mortality for men and women, suggesting that both are necessary for a complete picture of the aging process across genders.

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