title: Prospective longitudinal study of frailty transitions in a community-dwelling cohort of older adults with cognitive impairment.
abstract: 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.
authors.affiliation: Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S30843, Singapore, Singapore. Mei_Sian_Chong@ttsh.com.sg.|Department of Geriatric Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S308433, Singapore, Singapore. Mei_Sian_Chong@ttsh.com.sg.
authors.forename: Mei Sian
authors.initials: MS
authors.lastname: Chong
authors.affiliation: Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S30843, Singapore, Singapore. Laura_Tay@ttsh.com.sg.|Department of Geriatric Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S308433, Singapore, Singapore. Laura_Tay@ttsh.com.sg.
authors.forename: Laura
authors.initials: L
authors.lastname: Tay
authors.affiliation: Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S30843, Singapore, Singapore. Peng_Chew_Chan@ttsh.com.sg.|Department of Geriatric Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S308433, Singapore, Singapore. Peng_Chew_Chan@ttsh.com.sg.
authors.forename: Mark
authors.initials: M
authors.lastname: Chan
authors.affiliation: Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S30843, Singapore, Singapore. Wee_shiong_lim@ttsh.com.sg.|Department of Geriatric Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S308433, Singapore, Singapore. Wee_shiong_lim@ttsh.com.sg.
authors.forename: Wee Shiong
authors.initials: WS
authors.lastname: Lim
authors.affiliation: Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S30843, Singapore, Singapore. ruijing_ye@ttsh.com.sg.
authors.forename: Ruijing
authors.initials: R
authors.lastname: Ye
authors.affiliation: Department of Neurology, Singapore General Hospital, Outram Rd, S169608, Singapore, Singapore. tan.eng.king@sgh.com.sg.|Duke-NUS Graduate Medical School, 8 College Road, S169857, Singapore, Singapore. tan.eng.king@sgh.com.sg.
authors.forename: Eng King
authors.initials: EK
authors.lastname: Tan
authors.affiliation: Institute of Geriatrics and Active Ageing, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S30843, Singapore, Singapore. Yew_Yoong_Ding@ttsh.com.sg.|Department of Geriatric Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, S308433, Singapore, Singapore. Yew_Yoong_Ding@ttsh.com.sg.
authors.forename: Yew Yoong
authors.initials: YY
authors.lastname: Ding
mesh_terms: D000368:Aged; D060825:Cognitive Dysfunction / Q000523:psychology* / Q000534:rehabilitation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D016330:Frail Elderly / Q000523:psychology*; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies