Prospective longitudinal study of frailty transitions in a community-dwelling cohort of older adults with cognitive impairment.

BACKGROUND: Frailty and cognitive impairment are seemingly distinct syndromes, but have a shared vulnerability to stress in older adults, resulting in poorer outcomes. Although there has been recent interest in cognitive frailty, frailty transitions in relation to cognitive deterioration in older adults with cognitive impairment have not yet been well studied. We thus aim to study frailty transitions and change in cognitive status over 1-year follow-up among subjects with cognitive impairment attending a tertiary Memory Clinic. METHODS: This is a prospective cohort study of mild cognitive impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling subjects. We obtained data on clinical measures, muscle mass and physical performance measures. Cognitive status was measured using Chinese Mini-Mental State Examination (CMMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. We measured gait speed, hand grip strength, exhaustion and weight loss at baseline, 6 and 12 months to classify subjects according to the modified Fried criteria (involving strength, gait speed, body composition and fatigue) into non-frail (<2 frail categories) and frail categories (≥2 frail categories). Frailty transitions between baseline and 12-months were assessed. We performed random effects statistical modelling to ascertain baseline predictors of longitudinal frailty scores for all subjects and within MCI subgroup. RESULTS: Among 122 subjects comprising 41 MCI, 67 mild and 14 moderate AD, 43.9, 35.8 and 57.1% were frail at baseline respectively. Frailty status regressed in 32.0%, remained unchanged in 36.0%, and progressed in 32.0 % at 12 months. Random effects modelling on whole group showed longitudinal CDR-SB scores (coeff 0.09, 95% confidence interval (CI) 0.03-0.15) and age (coeff 0.04, 95 % CI 0.02-0.07) to be significantly associated with longitudinal frailty score. Among MCI subjects, only female gender (coeff 1.28, 95 % CI 0.21-2.36) was associated with longitudinal frailty score, while mild-moderate AD subjects showed similar results as those of the whole group. CONCLUSIONS: This is the first study to show longitudinal frailty state transitions in cognitively-impaired older adults. Frailty transitions appear to be independent of progression in cognitive status in earliest stages of cognitive impairment, while mild-moderate AD subjects showed associations with age and cognitive deterioration. The potential for cognitive frailty as a separate therapeutic entity for future physical frailty prevention requires further research with a suitably powered study over a longer follow-up period.

The Case for Stage-Specific Frailty Interventions Spanning Community Aging to Cognitive Impairment.

OBJECTIVES: To explore factors associated with frailty across the continuum of healthy aging to cognitive impairment (mild cognitive impairment [MCI], mild and moderate Alzheimer disease [AD]). DESIGN: Cross-sectional study. SETTING: Senior activity centers and the outpatient memory clinic of a tertiary hospital. PARTICIPANTS: Community-dwelling and functionally independent adults aged 50 years and older and older adults attending the memory clinic with MCI, and mild and moderate AD diagnoses. METHODS: We recruited 299 participants comprising 200 cognitively healthy individuals, 16 with MCI, 68 with mild AD, and 15 with moderate AD. We collected measures of comorbidities, cognitive and functional performance, physical activity level, and anthropometric and nutritional status. Frailty was defined using Buchmann criteria, and sarcopenic obesity (SO) was defined using the Asian Working Group for Sarcopenia criteria and the revised National Cholesterol and Education Panel-obesity definition of waist circumference. Multiple logistic regression was performed to identify factors associated with frailty as a whole group and separately based on cognitive subgroups. RESULTS: There were 16.7% of patients who met frailty criteria. Frailty prevalence was lowest in the well elderly (3.5%) and subsequently followed a U-shaped prevalence from MCI to mild and moderate AD, respectively. Specific univariate differences were noted in age, hypertension, ischemic heart disease, depressive symptoms, social differences, and functional scores. Multivariable logistic regression showed age, cognitive status, and SO to be significantly associated with frailty status. Subgroup analysis showed only SO to be significant (odds ratio [OR] 15.55, 95% confidence interval [CI] 1.63-148.42) in well elderly and only cognition to be associated with frailty (OR 0.89, 95% CI 0.80-0.99) among the cognitively impaired. CONCLUSION: Our findings lend initial support to the case for stage-specific interventions for physical frailty with the focus on SO in healthy community-dwelling older persons and cognitive-based measures in older adults with cognitive impairment. The accurate clinical phenotyping would then set the stage for future potential investigative therapies along these specific lines, rather than an undifferentiated approach.