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Background: Frailty Index (FI) reflects health, functioning and well-being of older people. It is valuable to compare how frailty has changed over time in ageing cohorts. This study aims to examine trends in frailty among 75-95-year-old men and women over three decades., Methods: The Helsinki Ageing Study started in 1989 and includes repeated cross-sectional postal surveys every 10 years examining community-dwelling cohorts of older people (75, 80, 85, 90 and 95 years). FI comprises the same 36 items in each cohort., Results: The mean FI was 0.22 (SD 0.12), 0.25 (SD 0.15), 0.26 (SD 0.15) and 0.23 (SD 0.15) in 1989, 1999, 2009 and 2019, respectively (P for linearity for crude values .11). Adjusted for age and sex, the four cohorts differed in their frailty the 2019 cohort having the lowest FI. This sex-adjusted difference was seen among 75-, 80-, 85- and 90-year-olds but not among 95-year-olds. FI decreased more among men than women (P for cohort <.001, P for sex <.01, P for interaction = .19)., Conclusions: The prevalence of frailty among community-dwelling individuals aged 75, 80, 85 and 90 years-but not among those aged 95 years-has significantly decreased over the last decades. This positive trend may have important implications for health policies in societies with increasing longevity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: assessing cardiovascular and mortality risk with conventional biomarkers is challenging in oldest-old due to multimorbidity and polypharmacy. Ceramides are bioactive lipids shown to predict mortality in late middle-aged cohorts., Objective: to assess whether plasma ceramides have independent prognostic value for mortality among oldest-old (85+)., Design: longitudinal cohort study (Helsinki Businessmen Study, HBS) with a 3.5-year follow-up., Setting and Subjects: survivors of HBS (125 men born in 1919-1934) visited the clinic for laboratory and clinical examination., Methods: functional status including physical (short physical performance battery) and Montreal Cognitive Assessment (MoCA) cognitive performance was assessed and laboratory examinations included a large set of biomarkers. Plasma ceramide concentration (Cer(d18:1/16:0)) was measured using a targeted liquid chromatography-tandem mass spectrometry assay. Mortality was retrieved from national registers., Results: median age was 88 years, two-thirds had multimorbidity and 59% were on statin treatment. During the follow-up, 22 (18%) men died. In a model adjusted for variables associated with mortality in the whole cohort at P < 0.20 (log glucose, SPPB, MoCA and statin use), Cer(d18:1/16:0) as a continuous trait was associated with increased mortality: hazard ratio (HR) per 1 SD 1.64 (95% confidence interval [CI] 1.23-2.18). Compared with the bottom tertile of Cer(d18:1/16:0), HR of mortality was 5.44-fold (95% CI 1.17-25.3) in the top tertile., Conclusions: these data raise the hypothesis that plasma ceramide concentrations and especially Cer(d18:1/1:60) may offer a clinically useful biomarker to evaluate prognosis in very old age. Such biomarkers are needed for geriatrics, where multimorbidity and pharmacotherapies, such as statins are prevalent hampering assessment of prognosis using conventional methods., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Randomised controlled trials (RCTs) usually provide the best evidence for treatments and management. Historically, older people have often been excluded from clinical medication trials due to age, multimorbidity and disabilities. The situation is improving, but still the external validity of many trials may be questioned. Individuals participating in trials are generally less complex than many patients seen in geriatric clinics. Recruitment and retention of older participants are particular challenges in clinical trials. Multiple channels are needed for successful recruitment, and especially individuals experiencing frailty, multimorbidity and disabilities require support to participate. Cognitive decline is common, and often proxies are needed to sign informed consent forms. Older people may fall ill or become tired during the trial, and therefore, special support and empathic study personnel are necessary for the successful retention of participants. Besides the risk of participants dropping out, several other pitfalls may result in underestimating or overestimating the intervention effects. In nonpharmacological trials, imperfect blinding is often unavoidable. Interventions must be designed intensively and be long enough to reveal differences between the intervention and control groups, as control participants must still receive the best normal care available. Outcome measures should be relevant to older people, sensitive to change and targeted to the specific population in the trial. Missing values in measurements are common and should be accounted for when designing the trial. Despite the obstacles, RCTs in geriatrics must be promoted. Reliable evidence is needed for the successful treatment, management and care of older people., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dementia is a condition which results in a high cost of care, a significant proportion of which is the cost associated with informal care. In previous studies, informal caregiving has been challenging to assess due to difficulties in estimating the true time spent on caregiving work and how to value caregivers' time. The aim of this study was to compare the costs of dementia among patients living alone and among those living with a caregiver to show the monetary value of informal caregiving from a societal perspective., Methods: Data from our four dementia trials using the same measures were combined, allowing the inclusion of 604 participants. Participants were followed up for 2 years or until death for their use of health and social services. Use of all services was retrieved from medical/social records. We also included the costs of lost productivity of those caregivers who were not retired., Results: The total mean cost of services and lost productivity was €22,068/person-year (pyrs). Participants living alone had a mean cost of €45,156/pyrs, whereas those living with a spouse had a mean cost of €16,416/pyrs (mean cost ratio 2.99, 95% confidence interval 2.64-3.39). Participants living alone and having <15 Mini-Mental State Examination points had higher costs than people with dementia in institutional care., Conclusions: Detailed data of service use and characteristics of people with dementia showed that from a societal perspective, living alone is a very strong determinant of service use in dementia. Informal caregivers do invaluable work for society., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: statin treatment has increased also among people aged 80 years and over, but adverse effects potentially promoting frailty and loss of resilience are frequent concerns., Methods: in the Helsinki Businessmen Study, men born in 1919-34 (original n = 3,490) have been followed up since the 1960s. In 2011, a random subcohort of home-living survivors (n = 525) was assessed using questionnaires and clinical (including identification of phenotypic frailty) and laboratory examinations. A 7-year mortality follow-up ensued., Results: we compared 259 current statin users (median age 82 years, interquartile range 80-85 years) with 266 non-users (83; 80-86 years). Statin users had significantly more multimorbidity than non-users (prevalencies 72.1% and 50.4%, respectively, P < 0.0001) and worse glucose status than non-users (prevalencies of diabetes 19.0% and 9.4%, respectively, P = 0.0008). However, there was no difference in phenotypic frailty (10.7% versus 11.2%, P = 0.27), and statin users had higher plasma prealbumin level than non-users (mean levels 257.9 and 246.3 mg/L, respectively, P = 0.034 adjusted for age, body mass index and C-reactive protein) implying better nutritional status. Despite morbidity difference, age-adjusted 7-year mortality was not different between the two groups (98 and 103 men among users and non-users of statins, respectively, hazard ratio 0.96, 95% confidence interval 0.72-1.30)., Conclusions: our study suggests that male octogenarian statin users preserved resilience and survival despite multimorbidity, and this may be associated with better nutritional status among statin users., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: alcohol consumption has many harmful health effects, but also benefits of moderate consumption on frailty have been reported. We examined this relationship longitudinally from midlife to old age., Methods: data of reported alcohol consumption in midlife (year 1974) and in old age (years 2000 and 2003) were available of a socioeconomically homogenous sample of 2360 men (born 1919-34, the Helsinki Businessmen Study). Alcohol consumption was divided into zero (N = 131 at baseline), light (1-98 g/week, N = 920), moderate (99-196, N = 593), and high consumption (>196, n = 716). Incidence of phenotypic frailty and prefrailty was assessed in 2000 and 2003. Alcohol consumption (reference 1-98 g/week, adjusted for age, body mass index and smoking) was related to frailty both longitudinally (from 1974 to 2000, and from 2000 to 2003) and cross-sectionally in 2000 and 2003., Results: during a 30-year follow-up, high consumption clearly decreased whereas lighter consumption remained stable. High consumption in midlife predicted both frailty (odds ratio = 1.61, 95% confidence interval = 1.01-2.56) and prefrailty (1.42; 1.06-1.92) in 2000, association with zero and moderate consumption was insignificant. Cross-sectionally in 2000, both zero (2.08; 1.17-3.68) and high consumption (1.83; 1.07-3.13) were associated with frailty, while in 2003 only zero consumption showed this association (2.47; 1.25-4.88)., Conclusion: the relationship between alcohol and frailty is a paradox during the life course. High, not zero, consumption in midlife predicts old age frailty, while zero consumption in old age is associated with frailty, probably reflecting reverse causality., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com)

Background: Long working hours and short sleep duration are associated with a range of adverse health consequences. However, the combined effect of these two exposures on health-related quality of life (HRQoL) has not been investigated., Methods: We studied white men born between 1919 and 1934 in the Helsinki Businessmen Study (HBS, initial n = 3,490). Data on clinical variables, self-rated health (SRH), working hours and sleep duration in 1974, and RAND-36 (SF-36) HRQoL survey in the year 2000 were available for 1,527 men. Follow-up time was 26 years. By combining working hours and sleep duration, four categories were formed: (i) normal work (≤50 hours/week) and normal sleep (>47 hours/week); (ii) long work (>50 hours/week) and normal sleep; (iii) normal work and short sleep (≤47 hours/week); and (iv) long work and short sleep. The association with RAND-36 domains was examined using multiple linear regression models adjusted for age, smoking and SRH., Results: Compared to those with normal work and sleep in midlife, men with long work and short sleep had poorer RAND-36 scores for physical functioning, vitality and general health, and those with long work and normal sleep had poorer scores for physical functioning in old age. Adjustment for midlife smoking and SRH attenuated the associations, but the one for long work and short sleep and physical functioning remained significant (difference in mean physical functioning score −4.58, 95% confidence interval −9.00 to −0.15)., Conclusion: Businessmen who had long working hours coupled with short sleep duration in midlife had poorer physical health in old age., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: little is known about the oldest-olds' views on ageing., Objective: to investigate older people's desire and the reasons they give for wanting to live to 100., Design: a postal questionnaire, analysed both quantitatively and qualitatively., Setting: population based in Helsinki, Finland., Subjects: a random sample (response rate 64%; N = 1,405) of community-dwelling older people (aged 75-96)., Methods: a structured self-completed questionnaire with an open-ended question on the reasons why/why not participants wished/did not wish to live to 100., Results: one-third (32.9%) of home-dwelling older people wanted to live to be 100. Those who did were older, more often male and self-rated their health better than those who did not. Often the desire for long life was conditional: 'Yes, if I stay healthy'. Among the reasons is that many were curious to see what would happen. Many stated that they loved life, they had twinkle in their eye or significant life roles. Those who did not want to live extremely long lives gave various rationales: they would become disabled, life would be meaningless, they were reluctant to become a burden to others or they feared loss of autonomy or suffering pain or loneliness. Some people also shared the view that they should not intervene in destiny or they felt that they had accomplished what they wanted in life., Conclusions: one-third of the oldest-old participants wanted to live to 100. Identifying what motivated them to desire long life could be a resource in their care plans., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: high TSH concentrations and cognitive decline are both very common among older people and could be linked., Objective: to assess cognition in our cohort of 335 home-dwelling older people (75 years and older) and to cross-sectionally relate the results to thyroid-stimulating hormone (TSH) concentrations. Our special focus was on the upper normal TSH range and subclinical hypothyroidism., Methods: cognitive performance was evaluated using the Consortium to Establish a Registry for Alzheimer's disease neuropsychological battery (CERAD-nb). The Clinical Dementia Rating (CDR) scale was used to evaluate severity of cognitive disorder. The APOEε4 genotype was also defined. Subjects were divided into quartiles based on the TSH concentrations, and results were compared between these groups., Results: expected relations were observed between CERAD domains and both educational level and APOEε4 genotype. Female sex significantly associated with better performance in Boston naming (OR = 0.48; 95% CI = 0.27-0.85). In the whole cohort, higher TSH concentrations tended to associate with better scores in most parts of the CERAD-nb tests, but differences were not statistically significant. However, subjects with the highest TSH concentration (90th TSH percentile, range 4.14-14.4 mU/l) had better CDR scores compared with subjects with the lowest TSH concentration (10th percentile, range 0.001-0.63 mIU/l; OR 0.10; 95% CI 0.014-0.76)., Conclusions: our results do not support the notion that higher TSH concentrations, not even in the range of subclinical hypothyroidism, would adversely affect cognition among older people., (© The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: there is little research how older people's will-to-live predicts their survival., Objective: to investigate how many years home-dwelling older people wish to live and how this will-to-live predicts their survival., Methods: as a part of the Drugs and Evidence-Based Medicine in the Elderly (DEBATE) study, 400 home-dwelling individuals aged 75-90 were recruited into a cardiovascular prevention trial in Helsinki. In 2000, a questionnaire about the wishes of their remaining life was completed by 283 participants. Participants were inquired how many years they would still wish to live, and divided into three groups according to their response: group 1: wishes to live <5 years, group 2: 5-10 years, group 3: >10 years. Mortality was confirmed from central registers during a 10-year follow-up. The adjusted Cox proportional hazard model was used to determine how will-to-live predicted survival., Results: in group 1 wishing to live less than 5 years, the mean age and the Charlson comorbidity index were the highest, and subjective health the poorest. There were no differences between the groups in cognitive functioning or feeling depressed. Mortality was the highest (68.0%) among those wishing to live <5 years compared with those wishing to live 5-10 years (45.6%) or over 10 years (33.3%) (P < 0.001). With group 1 as referent (HR: 1.0) in the Cox proportional hazard model adjusting for age, gender, Charlson comorbidity index and depressive feelings, HR for mortality was 0.66 (95% CI: 0.45-0.95) (P = 0.027) and 0.47 (95% CI: 0.26-0.86) (P = 0.011) in groups 2 and 3, respectively., Conclusion: the will-to-live was a strong predictor for survival among older people irrespective of age, gender and comorbidities.