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Abstract: Background: Ageing is characteristically accompanied by changes in vascular endothelial markers and growth factor as well as increased cellular death. We analysed the associations of the plasma levels of vascular cell adhesion molecule-1 (VCAM-1), hepatocyte growth factor (HGF) and soluble Fas (sFAS), and their combinations, with 4-year mortality to identify new biomarkers. Methods: A total of 238 individuals, both community-dwelling and institutionalised, aged 89‒91years and participating in the Vitality 90+ study were included. Biomarkers of endothelial function (VCAM-1), growth factor (HGF) and a marker of apoptosis (sFAS) were determined from plasma using Luminex® technology. This newly-determined data was combined with earlier data, e.g., 4-year mortality and medical history. Results: Subjects who died during the follow-up had higher baseline plasma levels of VCAM-1, sFas, and HGF. When other known risk factors were adjusted for, subjects in the highest concentration tertile for VCAM-1 (HR 1.85; 95% CI, 1.12–3.05) and HGF (HR 2.22; 95% CI, 1.33–3.71) had higher mortality compared to those in the lowest tertile. In the adjusted analyses, when compared to subjects with none of the biomarkers in the highest concentration tertile, mortality was also higher when sFas and VCAM-1 were simultaneously (HR 2.03; 95% CI, 1.13–3.64) or all three were simultaneously (HR 3.63; 95% CI, 1.65–7.97) in the highest concentration tertile. Conclusions: Our results suggest that increased concentrations of these biomarkers, separately and in combination, associate with mortality among the aged and are prognostic markers of death. [Copyright &y& Elsevier]

Aims: To analyse whether transitions between care settings differ between municipalities in the last 2 years of life among older people in Finland. Methods: Data were derived from Finnish national registers, and include all those who died in 2002 and 2003 at the age of 70 or older except those living in very small municipalities (n=67,027). Data include admissions and discharges from health and social care facilities (university hospitals, general hospitals, health centres, residential care facilities) and time spent outside care facilities for 730 days prior to death. Three-level negative binomial regression analyses were performed to study the effect of municipal factors on (1) the total number of all care transitions, (2) the number of transitions between home and different care facilities, and (3) transitions between different care facilities. Results: The municipality of residence had only a minor effect on the total number of care transitions, but greater variation between municipalities was found when different types of care transition were examined separately. Largest differences were found in care transitions involving specialised care. Age structure, urbanity, and economic situation of the municipality had an impact on several different care transitions. Conclusion: The total number of care transitions in 2 final years of life was approximately similar irrespective of the municipality of residence, but the findings imply differences in transitioning specialised care. Potentially, this may suggest inequality between the municipalities, but more detailed studies are needed to confirm the factors underlying these differences. [ABSTRACT FROM PUBLISHER]

Background: information about the predictors of mortality among the oldest-old is limited. Also possible gender differences are poorly known.Objective: to examine the predictors of mortality among individuals aged 90 and older, focusing on differences between men and women. We also analysed gender differences in survival at different levels of mobility and activities in daily living (ADL).Design: this 9-year follow-up study is part of the Vitality 90+ study, a population-based study of people aged 90 and older.Subjects: all inhabitants aged 90 and older in the area of Tampere, Finland were contacted, irrespective of health or dwelling place. The study population consisted of 171 men and 717 women.Methods: data were collected with a mailed questionnaire asking questions concerning ADL and mobility, self-rated health, chronic conditions and socio-economic factors. The participation rate was 79%. Cox regression enter models were used for the analysis.Results: older age, male gender, disability in ADL and mobility, poor self-rated health and institutionalisation increased the risk of mortality in the total study group. In age-adjusted Cox regression models, ADL and mobility were stronger predictors in men than in women (gender interactions, P < 0.001). Among those who were partly but not totally dependent in ADL or mobility women survived longer than men.Conclusion: the same health indicators that are important at younger old age also predict mortality in the oldest-old. Disability increases the likelihood of death more in men than women. At a very old age, women survive longer with moderate disability than do men. [ABSTRACT FROM PUBLISHER]

Plasma cell-free DNA (cf- DNA) has recently emerged as a potential biomarker of aging, reflecting systemic inflammation, and cell death. In addition, it has been suggested that cf- DNA could promote autoinflammation. Because the total cf- DNA pool comprises different cf- DNA species, we quantified the plasma levels of gene-coding cf- DNA, Alu repeat cf- DNA, mitochondrial DNA (mt DNA) copy number, and the amounts of unmethylated and total cf- DNAs. We identified the relationships between these cf- DNA species and age-associated inflammation, immunosenescence, and frailty. Additionally, we determined the cf- DNA species-specific transcriptomic signatures in blood mononuclear cells to elucidate the age-linked leukocyte responses to cf- DNA. The study population consisted of n = 144 nonagenarian participants of the Vitality 90+ Study and n = 30 young controls. In the nonagenarians, higher levels of total and unmethylated cf- DNAs were associated with systemic inflammation and increased frailty. The mt DNA copy number was also directly correlated with increased frailty but not with inflammation. None of the cf- DNA species were associated with immunosenescence. The transcriptomic pathway analysis revealed that higher levels of total and unmethylated cf- DNAs were associated with immunoinflammatory activation in the nonagenarians but not in the young controls. The plasma mt DNA appeared to be inert in terms of inflammatory activation in both the nonagenarians and young controls. These data demonstrate that the plasma levels of total and unmethylated cf- DNA and the mt DNA copy number could serve as biomarkers of frailty. In addition, we suggest that circulating self- DNA, assessed as total or unmethylated cf- DNA, might aggravate immunoinflammatory reactivity in very old individuals. [ABSTRACT FROM AUTHOR]

Abstract: Aging is associated with a profound reduction of the immune capacity (i.e., immunosenescence), which is manifested as increased morbidity and mortality due to infectious diseases in the elderly. The association of cytomegalovirus (CMV) with several aging-associated phenomena has been extensively characterized, e.g., the accumulation of CD8+ nonproliferative, apoptosis-resistant memory cells that have lost the expression of the costimulatory molecule CD28. However, as the CMV seroprevalence is notably high in elderly individuals, the role of CMV-independent changes has been difficult to analyze. To address this question, we performed a transcriptomic analysis (Illumina Human HT12 microarray) of the peripheral blood mononuclear cells (PBMCs) in a cohort of 90-year-old individuals (CMV seronegative, n=6; CMV seropositive, n=140) using the PBMCs of young CMV-seronegative individuals (n=11) as the controls. The cell type distribution (CD3, CD4, CD8, CD28 and CD14) was analyzed using FACS. The data showed that the gene expression profiles of the CMV+ and CMV− nonagenarians were different compared to the CMV− controls. Compared to the CMV− controls, 667 genes showed altered expression in the CMV− nonagenarians, and 559 genes were altered in the CMV+ nonagenarians. Of these, 337 genes were common. An analysis of the canonical pathways revealed that the number of affected pathways was also different (42 in CMV−, 13 in CMV+; of these, 9 were common). Taken together, these results indicate that the CMV-dependent and CMV-independent changes in the aging of the immune system are fundamentally different. [Copyright &y& Elsevier]

Abstract: Objective: The congruence between self-rated global health (SRH) and proxy-rated global health (PRH), the factors associated with congruence between SRH and PRH, and their associations with mortality are examined using data from the Vitality 90+ study. Study Design and Setting: The data consist of 213 pairs of subjects—aged 90 years and older—and proxies. The relationship between SRH and PRH was analyzed by chi-square test and Cohen’s kappa. Logistic regression analysis was used to find out the factors that are associated with the congruence between health ratings. The association between SRH and PRH with mortality was studied using Cox proportional hazard models. Results: The subjects rated their health more negatively than the proxies. Kappa value indicated only slight congruence between SRH and PRH, and they also predicted mortality differently. Good self-reported functional ability was associated with congruence between SRH and PRH. Conclusions: The results imply that the evaluation processes of SRH and PRH differ, and the measures are not directly interchangeable. Both measures are useful health indicators in very old age but SRH cannot be replaced by PRH in analyses. [Copyright &y& Elsevier]

Background.: Recent studies have suggested that inflammation may play an important role in aging and the development of disabilities, but knowledge about its importance in the development of muscle weakness and functional disabilities in very old people is limited. This study examined associations between inflammatory markers and physical performance among nonagenarians. Methods. T he population-based sample consisted of 197 women and 65 men aged 90 years. Physical performance was assessed according to the Barthel Index, the chair stand, and handgrip strength. Plasma levels of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and C-reactive protein (CRP) were determined. Results. A gender-adjusted linear regression model showed that high levels of CRP, IL-6, and IL-1Ra were significantly associated with poor handgrip strength (p = .041, p = .023, p < .001, respectively). After adjustment for diseases, smoking and physical exercise high levels of IL-6 and IL-1Ra were still significantly associated with poor hand grip strength (p = .048, p = .004, respectively). In the gender-adjusted model, high levels of CRP, IL-6, and IL-1Ra were significantly associated with a worse Barthel Index (p = .009, p = .004, p = .004, respectively). High levels of CRP and IL-6 were still significantly associated with a worse Barthel Index after adjusted for diseases, smoking and physical exercise (p = .034, p = .041, respectively). In the chair stand, no significant association with inflammatory markers was found. Conclusions. Associations between high levels of inflammatory markers and worse handgrip strength as well as a worse Barthel Index result were evident among nonagenarians. However, the association with the chair stand was not significant. [ABSTRACT FROM PUBLISHER]

Epigenetic mechanisms such as DNA methylation (DNAm) have a central role in the regulation of gene expression and thereby in cellular differentiation and tissue homeostasis. It has recently been shown that aging is associated with profound changes in DNAm. Several of these methylation changes take place in a clock-like fashion, i.e. correlating with the calendar age of an individual. Thus, the epigenetic clock based on these kind of DNAm changes could provide a new biomarker for human aging process, i.e. being able to separate the calendar and biological age. Information about the correlation of the time indicated by this clock to the various aspects of immunosenescence is still missing. As chronic cytomegalovirus (CMV) infection is probably one of the major driving forces of immunosenescence, we now have analyzed the correlation of CMV seropositivity with the epigenetic age in the Vitality 90 + cohort 1920 (122 nonagenarians and 21 young controls, CMV seropositivity rates 95% and 57%, respectively). The data showed that CMV seropositivity was associated with a higher epigenetic age in both of these age groups (median 26.5 vs. 24.0 (p < 0.02, Mann–Whitney U-test) in the young controls and 76.0 vs. 70.0 (p < 0.01) in the nonagenarians). Thus, these data provide a new aspect to the CMV associated pathological processes. [ABSTRACT FROM AUTHOR]

Polymorphisms affecting the expression of matrix metalloproteinases (MMPs), i.e. proteolytic enzymes that degrade intercellular material, have been found at position -1607 (1G/2G) in MMP1 and at -1171 (5A/6A) in MMP3. Interestingly, elevated levels of MMP1 and MMP3 have been observed in the brains of Alzheimer’s disease (AD) patients and those of tissue inhibitors of MMPs in the cerebrospinal fluid of AD and Parkinson’s disease (PD) patients, suggesting a role for MMPs in these disorders. The aim was to investigate a possible association between the afore-mentioned MMP1 and MMP3 polymorphisms and the risk of developing AD or PD. The polymorphisms were genotyped in 97 AD, 52 PD and 101 control patients. We found an interaction between MMP3*5A and APOE #x03B5;4 alleles (P < 0.0001) which increases the risk of AD (OR: 23.7, 95% CI: 5.8–144.9, P < 0.0001) compared to those who possess neither MMP3*5A nor APOE #x03B5;4. In conclusion, our finding suggests that the MMP3 gene, especially together with APOE #x03B5;4, may contribute to the development of AD. [Copyright &y& Elsevier]

Plasma contains several bioactive molecules (RNA, DNA, proteins, lipids, and metabolites), which are well preserved in extracellular vesicles, that are involved in many types of cell-to-cell interactions, and are capable of modifying biological processes in recipient cells. To obtain information about the source of mRNA molecules present in the plasma, we analyzed the plasma extracellular RNA (exRNA) of healthy individuals using RNA-sequencing and compared it to that of the peripheral blood mononuclear cell (PBMCs) of the same individual. The resultant data indicates that large proportion of the transcripts in plasma are derived from cell types other than PBMCs. To assess aging-associated changes in the plasma exRNA composition, gene ontology enrichment analysis was performed, revealing a functional decline in biological processes as a result of aging. Additionally, plasma RNA levels were analyzed with differential expression analysis, revealing 10 transcripts with significant aging-associated changes. Thus, it seems that the plasma exRNA is not fully derived from the PBMCs. Instead, other cell types supply RNAs to constitute the plasma exRNA compartment. This was true in both the young and elderly individuals that were tested. Furthermore, the RNA content of the plasma showed significant changes due to aging, affecting important biological processes. • Plasma mRNAs are not mainly derived from PBMCs. • Plasma mRNA composition changes as a result of aging. • Mitochondrial RNA transcripts are most abundant transcripts observed in plasma. [ABSTRACT FROM AUTHOR]

Abstract: Interleukin-7 is a homeostatic cytokine that contributes to the maintenance of the T cell pool. It also has proinflammatory effects and is involved in the pathogenesis of autoimmune diseases. Due to its homeostatic effects, IL-7 has been proposed as a potential rejuvenation factor for the elderly immune system. We analyzed the correlation of plasma IL-7 concentrations and the proportions of different T cell populations in nonagenarians (n=163) participating in the Vitality 90+ study. Young individuals (n=35, aged 19–30years) were used as controls. The numbers of CD3+, CD14+, CD4+ and CD8+ cells and the expression of the CD28 costimulatory molecule on CD4+ and CD8+ lymphocyte subsets were analyzed using flow cytometry. The plasma IL-7 levels were significantly higher in the nonagenarians compared to the controls (7.86 vs. 5.74pg/ml, p=0.004). In the nonagenarians, plasma IL-7 levels correlated inversely with the proportion of CD3+ T cells and directly with the proportion of CD14+ monocytes and plasma C-reactive protein. No correlation was observed between plasma IL-7 levels and the proportions of CD4+CD28− or CD8+CD28− subsets. These results suggest that the IL-7 levels in nonagenarians do not have an inhibitory effect on the development of immunosenescence; rather they are associated with increased inflammation. [Copyright &y& Elsevier]

Purpose: To study the agreement on disease prevalence between survey data and national health register data among people aged over 90., Patients and Methods: The survey data were from the Vitality 90+ Study conducted among 1637 community dwellers and persons in long-term care aged 90 and over in Tampere, Finland. The survey was linked with two national health registers, including hospital discharge data and prescription information. The prevalence of 10 age-related chronic diseases was calculated for each data source and the agreement between the survey and the registers was estimated using Cohen's kappa statistics and positive and negative percent agreement., Results: The prevalence of most diseases was higher in the survey than in the registers. The level of agreement was highest when the survey was compared with information combined from both registers. Agreement was almost perfect for Parkinson's disease (ĸ=0.81) and substantial for diabetes (ĸ=0.75) and dementia (ĸ=0.66). For heart disease, hypertension, stroke, cancer, osteoarthritis, depression, and hip fracture, the agreement ranged from fair to moderate., Conclusion: Self-reported information on chronic diseases shows acceptable agreement with health register data to warrant the use of survey methods in population-based health studies among the oldest old. It is important to acknowledge the gaps in health registers when validating self-reported information against register data., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Halonen et al.)

Objectives: To examine trends in the prevalence of dementia and related comorbidities among the oldest old., Methods: Six repeated cross-sectional surveys were conducted between 2001 and 2018, each including all inhabitants aged over 90 in Tampere, Finland ( n = 5386). Co-occurring conditions and their time trends among participants with dementia were examined using logistic regression and generalized estimating equations., Results: The prevalence of dementia decreased from 47% in 2007 to 41% in 2018. Throughout the study period, depression was more common among people with dementia compared to those without. The prevalence of hypertension, diabetes, and osteoarthritis increased and the prevalence of depression decreased among people with dementia. The mean number of comorbidities increased from 2.0 in 2001 to 2.3 in 2018., Discussion: Dementia remains highly prevalent among the oldest old and it is accompanied by an increasing burden of comorbidities, posing a challenge to people with dementia, their caregivers, and care systems.

Background: The burden of dementia, multimorbidity, and disability is high in the oldest old. However, the contribution of dementia and comorbidities to functional ability in this age group remains unclear. We examined the combined effects of dementia and comorbidities on ADL and mobility disability and differences between dementia-related disability between 2001, 2010, and 2018., Methods: Our data came from three repeated cross-sectional surveys in the population aged 90 + in the Finnish Vitality 90 + Study. The associations of dementia with disability and the combined effects of dementia and comorbidity on disability adjusted for age, gender, occupational class, number of chronic conditions, and study year were determined by generalized estimating equations. An interaction term was calculated to assess differences in the effects of dementia on disability over time., Results: In people with dementia, the odds of ADL disability were almost five-fold compared to people with three other diseases but no dementia. Among those with dementia, comorbidities did not increase ADL disability but did increase mobility disability. Differences in disability between people with and without dementia were greater in 2010 and 2018 than in 2001., Conclusion: We found a widening gap in disability between people with and without dementia over time as functional ability improved mainly in people without dementia. Dementia was the main driver of disability and among those with dementia, comorbidities were associated with mobility disability but not with ADL disability. These results imply the need for strategies to maintain functioning and for clinical updates, rehabilitative services, care planning, and capacity building among care providers., (© 2023. The Author(s).)

Background: There are a very few studies focusing on the individual-based survival with a long follow-up time., Aim: To identify predictors and determine their joint predictive value for longevity using individual-based outcome measures., Methods: Data were drawn from Tampere Longitudinal Study on Aging (TamELSA), a study of individuals' age 60-89 years (N = 1450) with a mortality follow-up of up to 35 years. Two measures of longevity were used: the longevity difference (LD) and realized probability of dying (RPD), both of which compare each individual's longevity with their life expectancy as derived from population life tables. Independent variables were categorized into five domains: sociodemographic, health and functioning, subjective experiences, social activities, and living conditions. Linear regression models were used in three steps: bivariate analysis for each variable, multivariate analysis based on backward elimination for each domain, and one final model., Results: The most important predictors of both outcomes were marital status, years smoked regularly, mobility, self-rated health, endocrine and metabolic diseases, respiratory diseases, and unwillingness to do things or lack of energy. The explained variance in longevity was 13.8% for LD and 14.1% for RPD. This demonstrated a large proportion of unexplained error margins for the prediction of individual longevity, even though many known predictors were used., Discussion and Conclusions: Several predictors associated with longer life were found. Yet, on an individual level, it remains difficult to predict who will live longer than their age peers. The stochastic element in the process of aging and in death may affect this prediction., (© 2022. The Author(s).)

Purpose: Vitality 90+ is an ongoing population-based study with repeated cross-sectional data collections. The study was designed to examine trends in health, functioning, living conditions, quality of life and care needs among the oldest old in Finland., Participants: Nine mailed surveys have been conducted in the city of Tampere between 1995 and 2018. The first three surveys in 1995, 1996 and 1998 included all community-dwelling individuals aged 90 years or older; and the following six surveys in 2001, 2003, 2007, 2010, 2014 and 2018 covered all individuals in Tampere regardless of their living arrangements. In total, the surveys have included 5935 participants (8840 observations). Around 80% of the participants have been women. The participants' age range has been between 90 and 107 years., Findings to Date: The surveys have consistently asked the same questions over time, covering basic sociodemographic factors, morbidity, functioning, self-rated health (SRH), living arrangements, social relations, quality of life, care needs and providers of care. Survey data have been linked with national register data on health and social service use, mortality and medication. The main findings regarding the time trends show an increase in the proportion of people independent in activities of daily living and mobility. Along with improved functioning, the number of chronic conditions has increased, and SRH has shown a tendency to decline. In addition, we have found increasing occupational class inequalities in functioning and SRH over time., Future Plans: The next round of data collection will be completed by the end of 2022. The Vitality 90+ Study welcomes research collaborations that fall within the general aims of the project. The research data 1995-2014 are archived at the Finnish Social Science Data Archive and the data for years 2018 and 2022 will be archived in 2023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17-82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker., (© 2022. The Author(s).)

[This corrects the article DOI: 10.1007/s10433-022-00698-y.]., (© Springer Nature B.V. 2022.)

Overall progress in life expectancy (LE) depends increasingly on survival in older ages. The birth cohorts now reaching old age have experienced considerable educational expansion, which is a driving force for the social change and social inequality. Thus, this study examines changes in old age LE by educational attainment in the Nordic countries and aims to find out to what extent the change in national LEs is attributable to education-specific mortality and the shifting educational composition. We used national register data comprising total 65 + populations in Denmark, Finland, Norway and Sweden to create period life tables stratified by five-year age groups (65-90 +), sex and educational attainment. Difference in LE between 2001 and 2015 was decomposed into the contributions of mortality changes within each educational group and changes in educational composition. Increasing LE at all ages and in all educational groups coincided with persistent and growing educational inequalities in all countries. Most of the gains in LE at age 65 could be attributed to decreased mortality (63-90%), especially among those with low education, the largest educational group in most countries. The proportion of the increase in LE attributable to improved education was 10-37%, with the highest contributions recorded for women in Norway and Sweden. The rising educational levels in the Nordic countries still carry potential for further gains in national LEs. However, the educational expansion has contributed to uneven gains in LE between education groups, which poses a risk for the future increase of inequalities in LE., Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00698-y., Competing Interests: Conflicts of interestThe authors declare no conflicts of interest., (© The Author(s) 2022, corrected publication 2022.)

Background: Comorbidities have major implications for the care of people with dementia., Aim: To investigate the patterns of comorbidities in dementia in the last five years of life and how these patterns differed between three cohorts., Methods: The study included people who died at age 70 and above in 2001 (n = 13,717), 2007 (n = 34,750) and 2013 (n = 38,087) in Finland. ICD-10 morbidity data for a five-year period prior to death were extracted from national registers. Principal component analysis was employed to identify patterns for several morbidities. The associations of principal component scores with dementia were analysed using binary logistic regression. Linear regression was used to examine changes in the number of morbidities in patterns over time., Results: The morbidity patterns identified in the last years of life were (1) cardiometabolic disorders, (2) neurological, (3) cerebrovascular diseases and (4) musculoskeletal, thyroid and psychiatric disorders. Among the patterns, neurological and musculoskeletal, thyroid and psychiatric disorders were associated with dementia. The number of diagnoses in the cerebrovascular pattern increased and those in the musculoskeletal, thyroid and psychiatric pattern decreased over time., Discussion: Comorbidity patterns identified in this nationwide register study are largely in line with previous evidence. Time difference in these patterns provide crucial information for service planning., Conclusions: Comorbidities in dementia in the last years of life occur in patterns and change over time. More systematic monitoring and updated clinical guidelines are needed for the care of comorbidities with dementia., (© 2021. The Author(s).)

While it is known that those who are living their last years are frequent users of social and health services, research about medicines at the end of life is scarce. We examined whether the proportions of purchasers and the types of prescription medicines purchased during a 2-year period differed between community-dwelling old people who died (decedents) in 2002, 2006 or 2011 and old people who lived at least 2 years longer (survivors) in Finland. We also examined how those differences changed over time. The study population was identified from nationwide registers and consisted of 174,097 community-dwelling people who were 70 years of age or older. Of these, 81,893 were decedents and 92,204 survivors. Data on purchases of medicines were gathered from the Finnish prescription database. Along with descriptive analyses, binary logistic regression analysis was used to find the association between decedent status and the purchase of medicines in general and different categories of medicines in particular. Almost all community-dwelling decedents and survivors purchased medicines at least once during the 2-year period. Over time, the proportion of purchasers increased in both groups but especially among survivors, thereby reducing the differences between the groups. However, the probability of purchasing medicines in general and different categories of medicine in particular remained significantly higher for decedents than for survivors after adjustments. This study shows that purchases of medication are concentrated at the end of life, as is the use of social and health services. However, the differences between decedents and survivors diminish over time., (© The Author(s) 2019.)

Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

Background: The need for long-term care services increases with age. However, little is known about the predictors of long-term care (LTC) entry among the oldest old., Aims: Aim of this study was to assess predictors of LTC entry in a sample of men and women aged 90 years and older., Methods: This study was based on the Vitality 90 + Study, a population-based study of nonagenarians in the city of Tampere, Finland. Baseline information about health, functioning and living conditions were collected by mailed questionnaires. Information about LTC was drawn from care registers during the follow-up period extending up to 11 years. Cox regression models were used for the analyses, taking into account the competing risk of mortality., Results: During the mean follow-up period of 2.3 years, 844 (43%) subjects entered first time into LTC. Female gender (HR 1.39, 95% CI 1.14-1.69), having at least two chronic conditions (HR 1.24, 95% CI 1.07-1.44), living alone (HR 1.37, 95% CI 1.15-1.63) and help received sometimes (HR 1.23, 95% CI 1.02-1.49) or daily (HR 1.68, 95% CI 1.38-2.04) were independent predictors of LTC entry., Conclusion: Risk of entering into LTC was increased among women, subjects with at least two chronic conditions, those living alone and with higher level of received help. Since number of nonagenarians will increase and the need of care thereby, it is essential to understand predictors of LTC entry to offer appropriate care for the oldest old in future.

Introduction: The place of death is suggested as a quality indicator for end-of-life care. We investigated how the place of death changed between 1998 and 2013 among people with dementia., Methods: Data from the Finnish national health and social care registers were extracted for all people with dementia, who had died at 70 years old during these years ( N  = 140,034). Descriptive analysis and logistic regression analysis were conducted., Results: In 2013, the most common place of death was the primary care hospital (39.8%), followed by nursing home and sheltered housing with 24-hour assistance (20.5%). Dying at home was rare (8.1%). During the study years, dying in the hospital decreased while dying in sheltered housing with 24-hour assistance increased., Discussion: The place of death for people with dementia has changed from institutions to noninstitutional care facilities. Further research on noninstitutional care facilities' ability to provide high-quality care at the end of life is needed.

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

It has been theorized that life resources influence goal engagement. The aim of the present study was to examine whether personal characteristics, and socio-economic, social and health resources are associated with personal goal content in old age. The participants were 824 community-dwelling people aged 75-90 from the Life-Space Mobility in Old Age project. Personal goals were elicited using a revised version of the Personal Project Analysis in a structured interview. Cross-sectional bi- and multivariate analyses using logistic regression modelling were conducted. The results showed that the most commonly reported goals were health maintenance related. People with better health resources were more likely to report goals related to leisure-time, social and physical activities and less likely to report goals related to recovery of health. Those with poor social resources were at risk for having no personal goals in their lives. The results are in line with theorizing on the influence of life resources on goal setting in old age. Further longitudinal studies are needed on whether resource loss precedes goal modification, and how goal setting strategies influence both mental and physical well-being in old age.

Poor self-rated health is associated with increased risk of mortality, but no previous study has examined how long-term trajectories of self-rated health differ among people at risk of subsequent death compared to those who survive. Data were drawn from French occupational cohort (the GAZEL study, 1989-2010). This nested case-control study included 915 deceased men and women and 2578 controls matched for sex, baseline age, occupational grade and marital status. Self-rated health was measured annually and dichotomized into good versus poor health. Trajectories of poor self-rated health up to 15 years were compared among people who subsequently died to those who survived. Participants contributed to an average 10.3 repeated assessments of self-rated health. Repeated-measures log-binomial regression analysis with generalized estimating equations showed an increased prevalence of poor self-rated health in cases 13-15 years prior to death from ischemic and other cardiovascular disease [multivariable-adjusted risk ratio 2.06, 95 % confidence interval (CI) 1.55-2.75], non-smoking-related cancers (1.57, 95 % CI 1.30-1.89), and suicide (1.78, 95 % CI 1.00-3.16). Prior to death from ischemic and other cardiovascular disease, increased rates of poor self-rated health were evident even among persons who were free of cardiovascular diseases (2.05, 95 % CI 1.50-2.78). In conclusion, perceptions of health diverged between the surviving controls and the deceased already 15 years prior to death. For cardiovascular mortality, decline in self-rated health started before diagnosis of the disease leading to death. The findings suggest that declining self-rated health might capture pathological changes before and beyond the disease diagnosis.

Background: The associations of body mass index (BMI) and abdominal obesity with mortality among very old people are poorly known. The purpose of this study was to investigate the association of BMI, waist circumference (WC), and waist-to-hip ratio with mortality in nonagenarians., Methods: This study is part of a prospective population-based study, Vitality 90+, including both community-dwelling and institutionalized persons from Tampere, Finland. Altogether 192 women and 65 men aged 90 years were subjected to anthropometric measurements, a baseline interview, and a 4-year mortality follow-up. Cox proportional hazards models were used in the statistical analyses., Results: In men, normal weight indicated a three times higher mortality risk (hazard ratio [HR] 3.09, 95% confidence interval [CI] 1.35-7.06) compared with overweight, and WC was inversely associated with mortality (HR 0.96, 95% CI 0.93-1.00) after adjustment for covariates. In women, the univariate waist-to-hip ratio (HR 1.43, 95% CI 1.06-1.92) and BMI-adjusted waist-to-hip ratio (HR 1.45, 95% CI 1.07-1.97) were positively associated with mortality. Also, overweight women whose WC was <86 cm had lower mortality than normal weight women with similar WC (HR 0.34, 95% CI 0.12-0.97)., Conclusions: In nonagenarian men, low BMI and low WC predict increased mortality. In nonagenarian women, waist-to-hip ratio alone and adjusted for BMI is positively associated with mortality. The potential positive effects of overweight combined with WC warrant more detailed analyses in larger data. In all, future studies are needed to better understand the health and functional consequences of body composition among the oldest old.

Aims: To describe and analyse municipal differences in health and social service use among old people in the last 2 years of life., Methods: The data were derived from national registers. All those who died in 2002 or 2003 at the age of ≥ 70 years were included except those who lived in very small municipalities. The services included were different types of hospitals, long-term care, and home care. The variation in service use was described by coefficients of variation (CV). To analyse local differences, three-level (individual, municipal, and regional) binary logistic and Poisson regression analyses were performed., Results: A total of 67,027 decedents from 315 municipalities in 20 hospital districts were included. There was considerable variation in service use between residents of different municipalities, especially in the types of hospital used. Of the individual-level variables age and use of other services were associated (p < 0.05) with use of all services. Of the municipal-level variables, indicators describing the service pattern in the municipality were associated with use of all services and average age of decedents with most of the services. The presence of a university hospital in the hospital district increased the probability of using university and general hospitals, but among the users increased days in university hospital and decreased days in general hospital., Conclusions: Considerable differences between municipalities exist, but these cannot be exhaustively explained. Behind the differences are probably factors which are difficult to describe and quantify, such as historical developments and political realities.

Substantial growth of the population aged 90 years or over has focused interest on trends in the functioning and disability of the oldest old, but research findings are scarce and they vary. In the Vitality 90+ Study, we evaluated overall, gender-specific, and age-specific trends in disability among total cohorts of people aged 90 years or older in the city of Tampere, Finland, in the years 2001, 2003, and 2007. The size of the target population ranged from 1113 to 1146 and the participation rate from 79 to 86%. The participants were asked whether they were able to get in and out of bed, dress and undress, move about indoors, walk 400 m, and use stairs. Independence was defined as being able to perform an activity without help. The aggregate outcome measures included independence in all five activities, dependence in one to four activities, dependence in all five activities (severe dependence), and a disability score. In analyses taking into account the within subject associations which resulted due to those who participated in several years, and proxy respondents, no overall or gender-specific trend was found in any of the independence or dependence estimates. In each year, independence decreased clearly by increasing age. Our results imply stable disability levels in nonagenarians in a population with increasing life expectancy and improving survival until the age of 90. Longer-time series are needed to confirm the trends.

The goal of this research is to test whether often observed correlates of loneliness in older age are related to onset of loneliness longitudinally. Despite the increasing number of longitudinal studies, the investigation of factors that are related to onset of loneliness is still limited. Analyses are based on data of the TamELSA study, which is a population-based prospective study in Tampere, Finland and started in 1979. For the present study 469 older adults aged between 60 and 86 years at baseline, who were not lonely at baseline, were selected and followed-up in 1989, 1999 and 2006. During the 28 years of follow-up approximately one third (N = 178) of the study population developed feelings of loneliness. Logistic regression analyses indicated that losing a partner, reduced social activities, increased physical disabilities, increased feelings of low mood, uselessness and nervousness, rather than baseline characteristics, are related to enhanced feelings of loneliness at follow-up. The higher incidence of loneliness among women can be fully explained by the unequal distribution of risk factors among men and women (e.g., women more often become widowed). Our results are in line with the cognitive approach that conceptualizes loneliness as an unpleasant feeling due to a perceived discrepancy between the desired and the achieved level of social and personal resources.

The human immune system, especially the adaptive branch, substantially declines with ageing. Several distinct immunosenescent events have already been described, yet data regarding to age-associated baseline alterations in immune cell function is limited. Therefore, by using the TaqMan Human Immune Arrays we conducted a preliminary gene expression profiling of immune-related genes in the peripheral blood mononuclear cells of young individuals (aged 22–37 years, n = 13) and nonagenarians (n = 12), the latter being part of the Vitality 90+ Study. We also analysed the correlations between significantly regulated genes. The results revealed a significantly decreased expression of CCR7, CD19, CD28, CD40LG, ICOS, IL4, IL6 and LTA as well as significantly increased expression of FN1 in the nonagenarians as compared to the controls. Significant direct correlations were observed between the expression of CCR7 and CD19, CCR7 and ICOS, ICOS and CD19, ICOS and CD40LG, as well as CD40LG and CD28 in the nonagenarians but not in the controls. These results suggest that the key players of adaptive immunity i.e. the factors required for full lymphocyte activation are markedly and coordinately down-modulated in the very old individuals. Further research is, however, required to establish the relationship between these changes and the mechanisms of immunosenescence.

This study focuses on the amount and types of transitions in health and social service system during the last 2 years of life and the places of death and among Finnish people aged 70-79, 80-89 and 90 or older. The data set, derived from multiple national registers, consists of 75,578 people who died between 1998 and 2001. The services included university hospitals, general hospitals, health centres and residential care facilities. The most common place of death was the municipal health centre: half of the whole research population died in a health centre. The place of death varied by age and gender: men and people in younger age groups died more often in general or in university hospital or at home, while dying in health centres or in residential care homes was more common among women or the very old. Number of transitions varied from zero to over a hundred transitions during the last 2 years. Number of transitions increased as death approached. Men and younger age groups had more transitions than women and older age groups. Among men and younger age groups transitions between home and general or university hospital were common while transitions between home and health centre or residential care were more common to women and older people. The results indicate that municipal health centres have a major role as care providers as death approaches. Differences between gender and age in numbers and types of transitions were clear. Future research is needed to clarify the causes to these differences.

The association of self-rated health with mortality is well established but poorly understood. This paper provides new insights into self-rated health that help integrate information from different disciplines, both social and biological, into one unified conceptual framework. It proposes, first, a model describing the health assessment process to show how self-rated health can reflect the states of the human body and mind. Here, an analytic distinction is made between the different types of information on which people base their health assessments and the contextual frameworks in which this information is evaluated and summarized. The model helps us understand why self-ratings of health may be modified by age or culture, but still be a valid measure of health status. Second, based on the proposed model, the paper examines the association of self-rated health with mortality. The key question is, what do people know and how do they know what they know that makes self-rated health such an inclusive and universal predictor of the most absolute biological event, death. The focus is on the social and biological pathways that mediate information from the human organism to individual consciousness, thus incorporating that information into self-ratings of health. A unique source of information is provided by the bodily sensations that are directly available only to the individual him- or herself. According to recent findings in human biology, these sensations may reflect important physiological dysregulations, such as inflammatory processes. Third, the paper discusses the advantages and limitations of self-rated health as a measure of health in research and clinical practice. Future research should investigate both the logics that govern people's reasoning about their health and the physiological processes that underlie bodily feelings and sensations. Self-rated health lies at the cross-roads of culture and biology, therefore a collaborative effort between different disciplines can only improve our understanding of this key measure of health status.

Background: We used case-control design to compare utilization of health and social services between older decedents and survivors, and to identify the respective impact of age and closeness of death on the utilization of services., Methods: Data were derived from multiple national registers. The sample consisted of 56,001 persons, who died during years 1998-2000 at the age of > or = 70, and their pairs matched on age, gender and municipality of residence, who were alive at least 2 years after their counterpart's death. Data include use of hospitals, long-term care and home care. Decedents' utilization within 2 years before death and survivors' utilization in the same period of time was assessed in three age groups (70-79, 80-89 and > or = 90 years) and by gender., Results: Decedents used hospital and long-term care more than their surviving counterparts, but the time patterns were different. In hospital care the differences between decedents and survivors rose in the last months of the study period, whereas in long-term care there were clear differences during the whole 2-year period. The differences were smaller in the oldest age group than in younger age groups., Conclusion: Closeness of death is an important predictor of health and social service use in old age, but its influence varies between age groups. Not only the changing age structure, but also the higher average age at death affects the future need for services.

The aim of this study was to examine if there are differences in self-rated health (SRH) between older people in St. Petersburg, Russia, and Tampere, Finland. Two SRH measures were examined: a global measure without any frame of reference, and an age-comparative SRH with an explicitly elicited reference of age peers. The Tampere data, consisting of 737 60-89-year-old respondents, came from the Tampere Longitudinal Study on Ageing (TamELSA) in 1989. The St. Petersburg data, consisting of 1,168 people aged 60-89 years, came from the Planning of Medical and Social Services within Elder Care in St. Petersburg project (IPSE) in 2000. In both cities the data were collected by same structured questionnaire. Self-rated health, both global and comparative, was better in Tampere than in St. Petersburg when symptoms, chronic diseases and functional ability were adjusted for. Also, the association of chronic diseases with global SRH was different in St. Petersburg and Tampere. In addition to the real differences in the prevalence and seriousness of health problems, the differences in SRH may be caused by different ways of evaluating health. Our conclusion is that self-rated health is sensitive to cultural and social factors. Direct comparisons between different countries should be made with caution, and the differences in language use must be taken into account when interpreting the results.

Background and Objectives: Self-rated health is a widely used measure of health status, but its biologic foundations are poorly understood. We investigated the association of frequently used biomarkers with self-rated health, and the role of these biomarkers in the association of self-rated health with mortality., Methods: The relation of self-rated health to blood levels of albumin, white blood cell count, hemoglobin, HDL cholesterol, and creatinine was examined in a population-based sample of 4,065 men and women aged 71 years or older. A Cox proportional hazards model was used to determine the association of self-rated health with mortality during 4.9 years. Sociodemographic factors, diagnosed chronic conditions, and activities of daily living disability were controlled for in these analyses., Results: All the biomarkers showed a graded relationship with self-rated health. After adjusting for other indicators, hemoglobin and white cell count were significantly associated with fair or poor self-rated health. When biomarkers and other indicators were adjusted for, self-rated health still was a significant predictor of mortality., Conclusion: Self-rated health has a biologic basis, and it can be a sensitive barometer of physiologic states. Self-rated health is likely to predict mortality because it covers the spectrum of health conditions better than the variables measured in the study.

The purpose of this study was to examine whether older age is associated with increasing loneliness in people aged 60 and over. Data came from TamELSA, a population-based prospective longitudinal study in Tampere, Finland. The follow-up time was 20 years. Loneliness was measured by a single question--"Do you feel lonely?"--with the possible answers often, sometimes, or never. Cross-sectional analysis showed that the percentage of subjects feeling lonely increased toward older age groups, but in a multivariate analysis, only household composition and social participation were independently associated with loneliness. Longitudinal analysis showed that loneliness increased with higher age. Over a 10-year period, loneliness increased most in those who, at baseline, were married and living alone with their spouse. In conclusion, only a minority of older people continuously suffer from loneliness. Loneliness does increase with age, not because of age per se, but because of increasing disability and decreasing social integration.

Based on an analysis of extracts from 11 free-form written texts and 13 focused interviews with Finnish husbands who had given care to their demented wives, this study was aimed at finding out how husbands signify their action as spousal caregivers. The data were approached qualitatively from a social constructionistic point of view. Husbands' written material described their action of caregiving mainly in a passive voice that echoed duty and responsive agency. Analysis of the interview talk revealed a wider spectrum of voices and more agentive talk about caregiving. The results of the study challenge interpretations of men as either ineffective or capable caregivers and highlight, instead, the contextual nature of the way that men construct their agencies, depending upon the purposes and audiences of their narration.