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Introductionmultiple conditions in later life (multi-morbidity) is a major challenge for health and care systems worldwide, is of particular relevance for older people, but has not (until recently) received high priority as a topic for research. We have identified the top 10 research priorities from the perspective of older people, their carers, and health and social care professionals using the methods of a James Lind Alliance Priority Setting Partnership.Methodsin total, 354 participants (162 older people and carers, 192 health professionals) completed a survey and 15 older people and carers were interviewed to produce 96 ‘unanswered questions’. These were further refined by survey and interviews to a shortlist of 21 topics, and a mix of people aged 80+ living with three or more conditions, carers and health and social care providers to prioritised the top 10.Resultsthe key priorities were about the prevention of social isolation, the promotion of independence and physical and emotional well-being. In addition to these broad topics, the process also identified detailed priorities including the role of exercise therapy, the importance of falls (particularly fear of falling), the recognition and management of frailty and Comprehensive Geriatric Assessment.Conclusionthese topics provide a unique perspective on research priorities on multiple conditions in later life and complement existing UK and International recommendations about the optimisation of health and social care systems to deliver essential holistic models of care and the prevention and treatment of multiple co-existing conditions.

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.

Cytomegalovirus (CMV) seropositivity in adults has been linked to increased cardiovascular disease burden. Phenotypically, CMV infection leads to an inflated CD8 T-lymphocyte compartment. We employed a 8-colour flow cytometric protocol to analyse circulating T cells in 597 octogenarians from the same birth cohort together with NT-proBNP measurements and followed all participants over 7 years. We found that, independent of CMV serostatus, a high number of CD27−CD28+ CD8 EMRA T-lymphocytes (TEMRA) protected from all-cause death after adjusting for known risk factors, such as heart failure, frailty or cancer (Hazard ratio 0.66 for highest vs lowest tertile; confidence interval 0.51–0.86). In addition, CD27−CD28+ CD8 EMRA T-lymphocytes protected from both, non-cardiovascular (hazard ratio 0.59) and cardiovascular death (hazard ratio 0.65). In aged mice treated with the senolytic navitoclax, in which we have previously shown a rejuvenated cardiac phenotype, CD8 effector memory cells are decreased, further indicating that alterations in T cell subpopulations are associated with cardiovascular ageing. Future studies are required to show whether targeting immunosenescence will lead to enhanced life- or healthspan.

Objective Ageing is associated with changes in cognition in some, but not all domains. In young–old adults, defined as persons aged 65–84 years, baseline cognitive function has been shown to impact on cognitive trajectories. Whether similar patterns occur in the very-old, defined as persons aged 85 years and over, is not known. Methods Longitudinal changes (5 years' follow-up) in global and domain specific cognitive function including memory, attention and speed were investigated in participants from the Newcastle 85+ Study (n = 845). At baseline, participants were grouped using Mini-Mental State Examination cut-off scores and dementia status into the following: not impaired, mildly impaired or severely impaired/dementia groups. Results Only a limited number of cognitive measures showed significant decline in performance over time. Where observed, change generally occurred only in the severely impaired group. In the severely impaired group, small differences in baseline age were associated with poorer performance over time on most measures. Education was not protective against cognitive decline in any group. Conclusions There are individuals who maintain a high level of cognitive function or only show mild impairments even into their ninth decade of life. This group of successful cognitive agers may provide insight for identifying predictors of cognitive integrity in later life. In individuals with severe impairment, cognitive performance shows significant decline over time, especially in measures of attention and speed. Further work to identify those individuals at highest risk of cognitive decline is necessary to implement early support and intervention strategies in this rapidly expanding age group. © 2017 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

A number of socio-economic, biological and lifestyle characteristics change with advancing age and place very old adults at increased risk of micronutrient deficiencies. The aim of this study was to assess vitamin and mineral intakes and respective food sources in 793 75-year-olds (302 men and 491 women) in the North-East of England, participating in the Newcastle 85+ Study. Micronutrient intakes were estimated using a multiple-pass recall tool (2×24 h recalls). Determinants of micronutrient intake were assessed with multinomial logistic regression. Median vitamin D, Ca and Mg intakes were 2·0 (interquartile range (IQR) 1·2–6·5) µg/d, 731 (IQR 554–916) mg/d and 215 (IQR 166–266) mg/d, respectively. Fe intake was 8·7 (IQR 6·7–11·6) mg/d, and Se intake was 39·0 (IQR 27·3–55·5) µg/d. Cereals and cereal products were the top contributors to intakes of folate (31·5 %), Fe (49·2 %) and Se (46·7 %) and the second highest contributors to intakes of vitamin D (23·8 %), Ca (27·5 %) and K (15·8 %). More than 95 % (n756) of the participants had vitamin D intakes below the UK’s Reference Nutrient Intake (10 µg/d). In all, >20 % of the participants were below the Lower Reference Nutrient Intake for Mg (n175), K (n238) and Se (n418) (comparisons with dietary reference values (DRV) do not include supplements). As most DRV are not age specific and have been extrapolated from younger populations, results should be interpreted with caution. Participants with higher education, from higher social class and who were more physically active had more nutrient-dense diets. More studies are needed to inform the development of age-specific DRV for micronutrients for the very old.

Background People aged 85 years and older are the fastest growing age group worldwide. This study assessed respiratory health, prevalence of respiratory disease and use of spirometry in respiratory diagnosis in a population-based cohort of 85 year olds to better understand respiratory health and disease in this sector of society. Methods A single year birth-cohort of 85 year olds participated in a respiratory assessment at their home or residential institution including self-reporting of symptoms and measurement of spirometry. General practice medical records were reviewed for respiratory diagnoses and treatments. Findings In the 845 participants, a substantial burden of respiratory disease was seen with a prevalence of COPD in medical records of 16.6% (n=140). A large proportion of the cohort had environmental exposures through past or current smoking (64.2%, n=539) and occupational risk factors (33.6%, n=269). Spirometry meeting reliability criteria was performed in 87% (n=737) of participants. In the subgroup with a diagnosis of COPD (n=123), only 75.6% (n=93) satisfied Global Initiative in Obstructive Lung Disease (GOLD) criteria for airflow obstruction, and in a healthy subgroup without respiratory symptoms or diagnoses (n=151), 44.4% (n=67) reached GOLD criteria for airflow obstruction and 43.3% (n=29) National Institute of Health and Care Excellence criteria for at least moderate COPD. Interpretation Spirometry can be successfully performed in the very old, aged 85 years, and may help identify respiratory diseases such as COPD. However interpretation in this age group using current definitions of COPD based on spirometry indices may be difficult and lead to overdiagnosis in a healthy group with transient symptoms.

Old age is often characterised as being associated with neglect, isolation and loneliness, not least since established risks factors for loneliness include widowhood, living alone, depression and being female. Cross-sectional data have challenged the notion that loneliness is especially an old-age phenomenon but longitudinal data on loneliness is scarce. Moreover, an under-represented group in prior studies are the oldest old, those aged 85 years and more. This paper addresses these knowledge gaps using data from the Newcastle 85+ Study, a large population-based cohort aged 85 years at first interview with follow-up interviews at 18 months and three years. At baseline over half (55%) reported being always or often alone, and 41 per cent reported feeling more lonely than ten years previously, although only 2 per cent reported always feeling lonely. Women spent more time alone than men and reported more loneliness both currently and compared to the past. Length of widowhood was a key factor, with those recently widowed having twice the risk of feeling lonely and those widowed for five or more years having a lower risk of reporting increased loneliness. Overall, the findings show that loneliness is a minority experience in the oldest old but is strongly driven by length of widowhood, challenging the notion that loneliness in later life is a static experience.

Bioelectrical impedance is a non-invasive technique for the assessment of body composition; however, information on its accuracy in the very old (80+ years) is limited. We investigated whether the association between the impedance index and total body water (TBW) was modified by hydration status as assessed by haematocrit and serum osmolarity. This was a cross-sectional analysis of baseline data from the Newcastle 85+ Cohort Study. Anthropometric measurements [weight, height (Ht)] were taken and body mass index (BMI) calculated. Leg-to-leg bioimpedance was used to measure the impedance value (Z) and to estimate fat mass, fat free mass and TBW. The impedance index (Ht2/Z) was calculated. Blood haematocrit, haemoglobin, glucose, sodium, potassium, urea and creatinine concentrations were measured. Serum osmolarity was calculated using a validated prediction equation. 677 men and women aged 85 years were included. The average BMI of the population was 24.3±4.2kg/m2 and the prevalence of overweight and obesity was 32.6% and 9.5%, respectively. The impedance index was significantly associated with TBW in both men (n=274, r=0.76, p

OBJECTIVES: to examine the association between subjective and objective measures of sleep and wake and other health parameters in a cohort of the very old. DESIGN: a population-based cohort study. SETTING: primary care, North East England.Participants: four hundred and twenty-one men and women, aged 87-89, recruited to the Newcastle 85+ Study cohort. METHODS: sleep questionnaires were administered and sleep-wake patterns were assessed over 5-7 days with a novel wrist triaxial accelerometer. Associations between sleep measures and various health parameters, including mortality at 24 months, were examined. RESULTS: only 16% of participants perceived their sleep as severely disturbed as assessed with questionnaire responses. Wrist accelerometry showed marked variation between normal and abnormal sleep-wake cycles that did not correlate with the participants' perception of sleep. Impaired sleep-wake cycles were significantly associated with cognitive impairment, disability, depression, increased falls, body mass index and arthritis but not with any other specific disease markers and with decreased survival. CONCLUSIONS: commonly used sleep questionnaires do not differentiate well between those with objectively determined disturbance of sleep-wake cycles and those with normal cycles. Abnormal sleep-wake patterns are associated with institutionalisation, cognitive impairment, disability, depression and arthritis but not with other diseases; there is also an association with reduced survival. Language: en

Context: Perturbations in thyroid function are common in older individuals but their significance in the very old is not fully understood. Objective: This study sought to determine whether thyroid hormone status and variation of thyroid hormones within the reference range correlated with mortality and disability in a cohort of 85-year-olds. Design: A cohort of 85-year-old individuals were assessed in their own homes (community or institutional care) for health status and thyroid function, and followed for mortality and disability for up to 9 years. Setting and Participants: Six hundred and forty-three 85-year-olds registered with participating general practices in Newcastle and North Tyneside, United Kingdom. Main Outcomes: All-cause mortality, cardiovascular mortality, and disability according to thyroid disease status and baseline thyroid hormone parameters (serum TSH, FT4, FT3, and rT3). Models were adjusted for age, sex, education, body mass index, smoking, and disease count. Results: After adjustment for age and sex, all-cause mortality was associated with baseline serum rT3 and FT3 (both P < .001), but not FT4 or TSH. After additional adjustment for potential confounders, only rT3 remained significantly associated with mortality (P = .001). Baseline serum TSH and rT3 predicted future disability trajectories in men and women, respectively. Conclusions: Our study is reassuring that individuals age 85 y with both subclinical hypothyroidism and subclinical hyperthyroidism do not have a significantly worse survival over 9 years than their euthyroid peers. However, thyroid function tests did predict disability, with higher serum TSH levels predicting better outcomes. These data strengthen the argument for routine use of age-specific thyroid function reference ranges., In a cohort of 85 year olds, serum reverse T3 and FT3, but not TSH or FT4, predicted mortality over 9 years. TSH and reverse T3 predicted disability outcomes in men and women, respectively.

Objectives. To examine the extent and complexity of the morbidity burden in 85-year-olds; identify patterns within multimorbidity; and explore associations with medication and healthcare use.Participants. 710 men and women; mean (SD) age 85.5 (0.4) years.Methods. Data on 20 chronic conditions (diseases and geriatric conditions) ascertained from general practice records and participant assessment. Cluster analysis within the multimorbid sample identified subgroups sharing morbidity profiles. Clusters were compared on medication and healthcare use.Results. 92.7% (658/710) of participants had multimorbidity; median number of conditions: 4 (IQR 3–6). Cluster analysis (multimorbid sample) identified five subgroups sharing similar morbidity profiles; 60.0% (395/658) of participants belonged to one of two high morbidity clusters, with only 4.9% (32/658) in the healthiest cluster. Healthcare use was high, with polypharmacy (≥5 medications) in 69.8% (459/658). Between-cluster differences were found in medication count (p=0.0001); hospital admissions (p=0.022); and general practitioner (p=0.034) and practice nurse consultations (p=0.011). Morbidity load was related to medication burden and use of some, but not all, healthcare services.Conclusions. The majority of 85-year-olds had extensive and complex morbidity. Elaborating participant clusters sharing similar morbidity profiles will help inform future healthcare provision and the identification of common underlying biological mechanisms.

Objective Heart failure (HF) prevalence rises sharply among those aged 85 years and over. Previous population based echocardiographic studies of left ventricular (LV) dysfunction, the substrate for HF, have included only small numbers in this age group. We used domiciliary echocardiography to estimate the prevalence of LV systolic and diastolic dysfunction in 87–89 year olds and the proportion remaining undiagnosed. Design Cross sectional analysis of data from Newcastle 85+ Study. Setting Primary care, North-East England. Participants 376 men and women aged 87–89 years. Measures Domiciliary echocardiography was performed and LV systolic and diastolic function was graded. The presence of limiting dyspnoea was assessed by questionnaire. Previous diagnoses of HF were abstracted from general practice (GP) records. Results 32% of participants (119/376) had LV systolic dysfunction (ejection fraction (EF) ≤50%) and a further 20% (75/376) had moderate or severe LV diastolic dysfunction with preserved EF. Both echocardiographic assessment of LV function and dyspnoea status were available in 74% (278/376) of participants. Among these participants, limiting dyspnoea was present in approximately two thirds of those with significant (systolic or isolated moderate/severe diastolic) LV dysfunction. 84% (73/87) of participants with significant LV dysfunction and limiting dyspnoea did not have a pre-existing HF diagnosis in their GP records. Overall, 26% (73/278) of participants with both echocardiographic and dyspnoea data had undiagnosed, symptomatic, significant LV dysfunction. Conclusion Significant systolic and diastolic LV dysfunction is much commoner in community dwelling 87–89 year olds than previous studies have suggested. The majority are both symptomatic and undiagnosed.

Age-related frailty is an increasing societal challenge with growing emphasis on identifying its underlying pathophysiology and prospects for intervention. We report findings from the first comprehensive study of frailty and biomarkers of inflammation, immunosenescence and cellular ageing in the very old. Using cross-sectional data from the Newcastle 85+ Study (n = 845, aged 85), frailty was operationalized by the Fried and Rockwood models and biomarker associations explored using regression analysis. We confirmed the importance of inflammatory markers (IL-6, TNF-alpha, CRP, neutrophils) in frailty in the very old, previously established only in younger–old populations. Limited evidence was found for immunosenescence in frailty; although total lymphocyte count was inversely related, no association was found with the immune risk profile and the inverse associations observed with memory/naive CD8 T and B cell ratios were in the opposite direction to that expected. We found no association with frailty in the very old for CMV sero-positivity, telomere length, markers of oxidative stress or DNA damage and repair. The Fried and Rockwood frailty models measure different albeit overlapping concepts yet biomarker associations were generally consistent between models. Difficulties in operationalizing the Fried model, due to high levels of co-morbidity, limit its utility in the very old.

Background: cognitive test scores and visual acuity are strongly associated in older people. This may be due to poor vision limiting performance on cognitive tasks specifically requiring vision, or an association between visual and neurodegenerative disorders. Objective: to explore, using data from the Newcastle 85+ cohort study, the impact of sight impairment (SI) on Mini-Mental State Examination (MMSE) scores and whether reduced scores among SI participants are limited to tasks requiring vision. Results: of 839 participants aged 85 years, 44 (5.2%) were registered SI. Median (inter-quartile range) sMMSE scores were 25 (22–29) for SI and 28 (25–29) for non-SI participants (P = 0.006). SI participants had lower subscale scores on tasks requiring vision (P

Sensitive and specific biomarkers of ageing are needed to evaluate interventions to extend health span. However, there is growing evidence that information provided by candidate biomarkers may change with age itself. Little is yet known about the value of candidate biomarkers in those over 85 years, currently the fastest growing population sub-group in many countries. This study assessed a large panel of candidate biomarkers in a cohort of 85 years old by studying comparative associations with health status. Using a cross-sectional sample of 852 individuals aged 85, we performed uni- and multi-variable analyses of associations between 74 candidate biomarkers and 4 health-status measures: viz. multi-morbidity, cognitive impairment, disability and proximity to death as measured by mortality within 1.5 years. We defined as most informative any measures that were significantly associated with at least two of the health-status measures in multivariable analyses in this age group. 10 out of 74 tested candidates fulfilled this criterion, while several proposed biomarkers of ageing, notably inflammation and immune risk markers and telomere length, did not. As future data accrues on health outcomes within the cohort, it will become possible also to evaluate the predictive value of these and others of the candidate biomarkers.

OBJECTIVES: To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people. DESIGN: Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention. SETTING: The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group. PARTICIPANTS: Eighty-one community-dwelling individuals aged 85. MEASUREMENTS: Participant and researcher acceptability, completion rates, time taken, validity as cognitive measures, and psychometric utility. RESULTS: Participants randomized to computerized tests were less likely to rate the cognitive function tests as difficult (odds ratio (OR)=0.16, 95% confidence interval (CI)=0.07–0.39), stressful (OR=0.18, 95% CI=0.07–0.45), or unacceptable (OR=0.18, 95% CI=0.08–0.48) than those randomized to pencil-and-paper tests. Researchers were also less likely to rate participants as being distressed in the computer test group (OR=0.19, 95% CI=0.07–0.46). Pencil-and-paper tasks took participants less time to complete (mean±standard deviation 18±4 minutes vs 26±4 minutes) but had fewer participants who could complete all tasks (91% vs 100%). Both types of task were equally good measures of cognitive function. CONCLUSION: Computerized and pencil-and-paper tests are both feasible and useful means of assessing cognitive function in the oldest-old age group. Computerized tests are more acceptable to participants and administrators.

Objectives Older adults are a fast growing group in society and are at high risk of hypertension, cognitive decline and dementia. Antihypertensive drugs, particularly calcium channel blockers (CCB), have been associated with a decreased risk of cognitive decline and dementia. We used observational data to examine the association between antihypertensive drug class and change in cognitive function. Methods The Newcastle 85+ Study is a population-based cohort study recruiting individuals aged 85 (born in 1921) via general/family practices in Newcastle/North Tyneside, United Kingdom. Data, including blood pressure, antihypertensive drug use and cognitive function [assessed using the Standardized Mini-Mental State Exam (SMMSE)], were collected at baseline and 3-year follow-up. Results The study population comprised 238 participants with a diagnosis of hypertension, prescribed antihypertensive drug treatment and with baseline and follow-up SMMSE assessment. There was an association between CCB use and less cognitive decline over 3 years (rate of decline was lower by 1.29 SMMSE points (95% confidence interval 0.16-2.42; P = 0.03) compared with those taking other antihypertensive classes after adjustment for age, sex, years of education, baseline SMMSE score, smoking, BMI, baseline blood pressure, and incident cerebrovascular event. This finding was even stronger in the cognitively intact (SMMSE >24), wherein rate of cognitive decline was lower by 1.33 SMMSE points (95% confidence interval 0.30-2.37; P = 0.01), but was not seen for other antihypertensive classes. Conclusion Findings provide support for an association between CCB use and a lower rate of cognitive decline in very old adults with hypertension.

Background The relationship between age-related frailty and the underlying processes that drive changes in health is currently unclear. Considered individually, most blood biomarkers show only weak relationships with frailty and ageing. Here, we examined whether a biomarker-based frailty index (FI-B) allowed examination of their collective effect in predicting mortality compared with individual biomarkers, a clinical deficits frailty index (FI-CD), and the Fried frailty phenotype. Methods We analyzed baseline data and up to 7-year mortality in the Newcastle 85+ Study (n = 845; mean age 85.5). The FI-B combined 40 biomarkers of cellular ageing, inflammation, haematology, and immunosenescence. The Kaplan-Meier estimator was used to stratify participants into FI-B risk strata. Stability of the risk estimates for the FI-B was assessed using iterative, random subsampling of the 40 FI-B items. Predictive validity was tested using Cox proportional hazards analysis and discriminative ability by the area under receiver operating characteristic (ROC) curves. Results The mean FI-B was 0.35 (SD, 0.08), higher than the mean FI-CD (0.22; SD, 0.12); no participant had an FI-B score

Background Guidelines advocate using B-type natriuretic peptides in the diagnostic work-up of suspected heart failure (HF). Their main role is to limit echocardiography rates by ruling out HF/LV dysfunction where peptide level is low. Recommended rule-out cut points vary between guidelines. The utility of B-type natriuretic peptides in the very old (85+) requires further investigation, with optimal cut points yet to be established. We examined NT-proBNP's utility, alone and in combination with history of myocardial infarction (MI), as a rule-out test for LV dysfunction in very old people with limiting dyspnoea. Methods Design: Cross-sectional analysis. Setting: Population-based sample; North-East England. Participants: 155 people (aged 87-89) with limiting dyspnoea. Measures: Dyspnoea assessed by questionnaire. Domiciliary echocardiography performed; LV systolic/diastolic function graded. NT-proBNP measured (Roche Diagnostics). Receiver operating characteristic analyses examined NT-proBNP's diagnostic accuracy for LV dysfunction. Results AUC for LVEF less than or equal to 50% was poor (0.58, 95% CI 0.49-0.65), but good for LVEF less than or equal to 40% (0.80, 95% CI 0.73-0.86). At ESC cut point (125ng/l), few cases of systolic dysfunction were missed (NPV 94-100%, depending on severity), but echocardiography (88%) and false positive rates (56-81 per 100 screened) were high. At NICE cut point (400ng/l), echocardiography (51%) and false positive rates (33-45) were lower; exclusionary performance was good for LVEF less than or equal to 40% (1 case missed per 100 screened, 15% of cases; NPV 97%), but poor for LVEF less than or equal to 50% (16 cases missed per 100 screened, 45% of cases; NPV 68%). Incorporating isolated moderate/severe diastolic dysfunction into target condition increased the proportion of cases missed (lower NPV), whilst improving case detection. Incorporating MI history as an additional referral prompt slightly reduced the number of cases missed at expense of higher echocardiography and false positive rates. Conclusions High echocardiography rates and poor exclusionary performance for mild degrees of systolic dysfunction and for diastolic dysfunction limit NT-proBNP's utility as a rule-out test for LV dysfunction in very old people with limiting dyspnoea. Incorporating MI history as an additional echocardiography prompt yields no overall benefit compared to using NT-proBNP level alone. Electronic supplementary material The online version of this article (doi:10.1186/1471-2261-14-128) contains supplementary material, which is available to authorized users.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. The genetic contribution to the variation in human lifespan is ∼ 25%. Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality. We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16 121 younger controls (

BackgroundExplanations for the male-female disability-survival paradox - that woman live longer than men but with more disability - include sex differences in diseases and their impact on disability and death. Less is known about the paradox in the very old. We examine sex differences in the presence and impact of disabling and fatal diseases accounting for the male-female disability-survival paradox in very late life.MethodsWe use data from the Newcastle 85+ Study, a cohort of people born in 1921 and all recruited at age 85 in 2006. Participants underwent a health assessment (HA) at baseline, 18 months, 36 months, 60 months, and a review of their GP records (GPRR) at baseline and 36 months. We used multi-state modelling to assess the impact of specific diseases on disability and death. Disability (measured via ADLs/IADLs) was categorised as no disability (difficulty with 0 activities), or disabled (difficulty with one or more activities). Diseases were ascertained from review of general practice records and cognitive impairment which was defined as an sMMSE of 21 or less (from health assessment).ResultsIn participants who had complete HA and GPRR, women had more arthritis (RR = 1.2, 95% CI: 1.1-1.3) and hypertension (RR = 1.2, 95%CI 1.0-1.3), more disability, and were more likely disabled at all follow-ups. From multistate models, women with cerebrovascular disease (HR: 2.6, 95% CI: 2.1-3.4) or respiratory disease (HR: 2.0, 95% CI: 1.4-3.0) were more likely to become disabled than those without but this did not hold for men (sex difference pConclusionThe disability-survival paradox was still evident at age 85 and appears due to sex differences in the types of diseases and their impact on the disability pathway.

Common age-related eye diseases including glaucoma, cataract and age-related macular degeneration (AMD) have been proposed to be associated with dementia. Few studies have examined the relationship between cognition and cataract or glaucoma. We explored the association between cognition and cataract and glaucoma diagnoses in community-dwelling 85-year-olds.Cross-sectional analysis of data from the Newcastle 85+ Study. Diagnoses of eye disease were extracted from family practice records. Cognitive performance was assessed by the standardized mini-mental state examination (sMMSE) and the sMMSE-blind (MMblind). Relationships between glaucoma diagnosis or cataract diagnosis and lower cognition were examined using ordinal logistic regression.Complete data were available for 839 participants. Of these, 36.0% (302/839) had recorded previous cataract surgery, 11.2% (94/839) untreated cataract and 7.9% (66/839) diagnosed glaucoma. Glaucoma diagnosis was associated with lower sMMSE results (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.05-2.95); but not lower MMblind (OR 1.17, 95% CI 0.65-2.12). When compared to no cataract, cataract diagnosis (treated and untreated combined) was associated with higher sMMSE (OR 0.55, 95% CI 0.38-0.79) and MMblind (OR 0.51, 95% CI 0.34-0.76). Previously treated cataract was associated with higher sMMSE (OR 0.72, 95% CI 0.59-0.88) and MMblind (OR 0.68, 95% CI 0.55-0.85). Untreated cataract was not significantly associated with sMMSE (OR 0.65, 95% CI 0.36-1.19) or MMblind (OR 0.73, 95% CI 0.39-1.36).This large epidemiological study of 85-year-olds found that lower sMMSE but not MMblind was associated with glaucoma diagnosis, suggesting the association may be driven by poor vision. Cataract diagnosis was associated with higher sMMSE and MMblind. Reasons for this observation are unclear but may relate to enhanced help-seeking behavior in people with diagnosed cataract.

INTRODUCTION: Falls are common in older people and increase in prevalence with advancing old age. There is limited knowledge about their impact in those aged 85 years and older, the fastest growing age group of the population. We investigated the prevalence and impact of falls, and the overlap between falls, dizziness and blackouts, in a population-based sample of 85 year olds. METHODS: Design: Cross-sectional analysis of baseline data from Newcastle 85+ Cohort Study. Setting: Primary care, North-East England. Participants: 816 men and women aged 85 years. Measurements: Structured interview with research nurse. Cost-consequence analysis of fall-related healthcare costs. RESULTS: Over 38% (313/816) of participants had fallen at least once in the previous 12 months and of these: 10.6% (33/312) sustained a fracture, 30.1% (94/312) attended an emergency department, and 12.8% (40/312) were admitted to hospital. Only 37.2% (115/309) of fallers had specifically discussed their falls problem with their general practitioner and only 12.7% (39/308) had seen a falls specialist. The average annual healthcare cost per faller was estimated at £202 (inter-quartile range £174-£231) or US$329 ($284-$377). 'Worry about falling' was experienced by 42.0% (128/305) of fallers, 'loss of confidence' by 40.0% (122/305), and 'going out less often' by 25.9% (79/305); each was significantly more common in women, odds ratios (95% confidence interval) for women: men of 2.63 (1.45-4.55), 4.00 (2.27-7.14), and 2.86 (1.54-5.56) respectively. Dizziness and blackouts were reported by 40.0% (318/796) and 6.4% (52/808) of participants respectively. There was marked overlap in the report of falls, dizziness and blackouts. CONCLUSIONS: Falls in 85 year olds are very common, associated with considerable psychological and physical morbidity, and have high impact on healthcare services. Wider use of fall prevention services is needed. Significant expansion in acute and preventative services is required in view of the rapid growth in this age group. Language: en

Objectives To investigate the order in which 85 year olds develop difficulty in performing a wide range of daily activities covering basic personal care, household care and mobility. Design Cross-sectional analysis of baseline data from a cohort study. Setting Newcastle upon Tyne and North Tyneside, UK. Participants Individuals born in 1921, registered with participating general practices. Measurements Detailed health assessment including 17 activities of daily living related to basic personal care, household care and mobility. Questions were of the form ‘Can you …’ rather than ‘Do you…’ Principal Component Analysis (PCA) was used to confirm a single underlying dimension for the items and Mokken Scaling was used to determine a subsequent hierarchy. Validity of the hierarchical scale was assessed by its associations with known predictors of disability. Results 839 people within the Newcastle 85+ study for whom complete information was available on self-reported Activities of Daily Living (ADL). PCA confirmed a single underlying dimension; Mokken scaling confirmed a hierarchic scale where ‘Cutting toenails’ was the first item with which participants had difficulty and ‘feeding’ the last. The ordering of loss differed between men and women. Difficulty with ‘shopping’ and ‘heavy housework’ were reported earlier by women whilst men reported ‘walking 400 yards’ earlier. Items formed clusters corresponding to strength, balance, lower and upper body involvement and domains specifically required for balance and upper/lower limb functional integrity. Conclusion This comprehensive investigation of ordering of ability in activities in 85 year olds will inform researchers and practitioners assessing older people for onset of disability and subsequent care needs.

Background Little is known of the capabilities of the oldest old, the fastest growing age group in the population. We aimed to estimate capability and dependency in a cohort of 85 year olds and to project future demand for care. Methods Structured interviews at age 85 with 841 people born in 1921 and living in Newcastle and North Tyneside, UK who were permanently registered with participating general practices. Measures of capability included were self-reported activities of daily living (ADL), timed up and go test (TUG), standardised mini-mental state examination (SMMSE), and assessment of urinary continence in order to classify interval-need dependency. To project future demand for care the proportion needing 24-hour care was applied to the 2008 England and Wales population projections of those aged 80 years and over by gender. Results Of participants, 62% (522/841) were women, 77% (651/841) lived in standard housing, 13% (106/841) in sheltered housing and 10% (84/841) in a care home. Overall, 20% (165/841) reported no difficulty with any of the ADLs. Men were more capable in performing ADLs and more independent than women. TUG validated self-reported ADLs. When classified by 'interval of need' 41% (332/810) were independent, 39% (317/810) required help less often than daily, 12% (94/810) required help at regular times of the day and 8% (67/810) required 24-hour care. Of care-home residents, 94% (77/82) required daily help or 24-hour care. Future need for 24-hour care for people aged 80 years or over in England and Wales is projected to increase by 82% from 2010 to 2030 with a demand for 630,000 care-home places by 2030. Conclusions This analysis highlights the diversity of capability and levels of dependency in this cohort. A remarkably high proportion remain independent, particularly men. However a significant proportion of this population require 24-hour care at home or in care homes. Projections for the next 20 years suggest substantial increases in the number requiring 24-hour care due to population ageing and a proportionate increase in demand for care-home places unless innovative health and social care interventions are found.

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity. In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.

Assessing food choice and/or nutrient intake in older people, particularly the oldest old (85 years and over), presents particular challenges. In some cases the respondent may have little or no involvement in food acquisition or preparation, in others, cognitive/memory impairment may restrict the ability to recall intake, or physical limitations may affect the ability to record intake. The assessment may therefore need to involve whoever provides care for the older person, of whom there may be more than one. For these reasons, there is a need for validated methods for dietary assessment in large populations within this age range. The need is particularly acute in view of the secular increase in the numbers of older people and the interest in the role of nutrition in maintaining health and ameliorating age-related decline. This paper describes a comparison of two different methods of dietary assessment within the Newcastle 85+ Study; a UK cohort study of health and ageing in the oldest old. Two methods, the food frequency questionnaire (FFQ) (based on broad recall of the previous 12 months intake) and the repeated multiple pass recall (MPR) tool (based on detailed recall of the previous day's intake on two separate occasions), were applied in two different groups of approximately 85 individuals aged 85 years. FFQ data were collected during a pilot study conducted between 2003 and 2004, MPR data were collected in the main Newcastle study in 2006. Relative validity was measured by calculation of the ratio of reported energy intake to estimated basal metabolic rate (EI/BMR) and by comparison with dietary intakes reported for subjects of similar age in the UK National Diet and Nutrition Survey. EI/BMR ratios for MPR were 1.56 and 1.39 for men and women, respectively, and for FFQ were 2.18 and 2.14. The FFQ was found to overestimate energy and nutrient intake considerably. The MPR gave more realistic estimates of energy and nutrient intakes, and was found to be acceptable for use in this population group. However, use of this tool required greater investigator (nurse) time, extra resources for training and quality assurance and additional time and expertise in data processing. In the Newcastle 85+ Study, where the overall aims include detailed investigation of diet in relation to many variables describing biological, clinical and psychosocial status, we concluded that MPR was the preferable method, although there remains a need for non-subjective methods for assessing dietary intake, that is, biomarker approaches, which can give a comprehensive and objective assessment of dietary exposure.

To compare the acceptability and feasibility of computerized and pencil-and-paper tests of cognitive function in 85-year-old people.Group comparison of participants randomly allocated to pencil-and-paper (Wechsler Adult Intelligence and Memory Scales) or computerized (Cognitive Drug Research) tests of verbal memory and attention.The Newcastle 85+ Pilot Study was the precursor to the Newcastle 85+ Study a United Kingdom Medical Research Council/Biotechnology and Biological Sciences Research Council cohort study of health and aging in the oldest-old age group.Eighty-one community-dwelling individuals aged 85.Participant and researcher acceptability, completion rates, time taken, validity as cognitive measures, and psychometric utility.Participants randomized to computerized tests were less likely to rate the cognitive function tests as difficult (odds ratio (OR)=0.16, 95% confidence interval (CI)=0.07-0.39), stressful (OR=0.18, 95% CI=0.07-0.45), or unacceptable (OR=0.18, 95% CI=0.08-0.48) than those randomized to pencil-and-paper tests. Researchers were also less likely to rate participants as being distressed in the computer test group (OR=0.19, 95% CI=0.07-0.46). Pencil-and-paper tasks took participants less time to complete (mean+/-standard deviation 18+/-4 minutes vs 26+/-4 minutes) but had fewer participants who could complete all tasks (91% vs 100%). Both types of task were equally good measures of cognitive function.Computerized and pencil-and-paper tests are both feasible and useful means of assessing cognitive function in the oldest-old age group. Computerized tests are more acceptable to participants and administrators.

Background The UK, like other developed countries, is experiencing a marked change in the age structure of its population characterised by increasing life expectancy and continuing growth in the older fraction of the population. There is remarkably little up-to-date information about the health of the oldest old (over 85 years), demographically the fastest growing section of the population. There is a need, from both a policy and scientific perspective, to describe in detail the health status of this population and the factors that influence individual health trajectories. For a very large proportion of medical conditions, age is the single largest risk factor. Gaining new knowledge about why aged cells and tissues are more vulnerable to pathology is likely to catalyse radical new insights and opportunities to intervene. The aims of the Newcastle 85+ Study are to expose the spectrum of health within an inception cohort of 800 85 year-olds; to examine health trajectories and outcomes as the cohort ages and their associations with underlying biological, medical and social factors; and to advance understanding of the biological nature of ageing. Methods A cohort of 800 85 year olds from Newcastle and North Tyneside will be recruited at baseline and followed until the last participant has died. Eligible individuals will be all those who turn 85 during the year 2006 (i.e. born in 1921) and who are registered with a Newcastle or North Tyneside general practice. Participants will be visited in their current residence (own home or institution) by a research nurse at baseline, 18 months and 36 months. The assessment protocol entails a detailed multi-dimensional health assessment together with review of general practice medical records. Participants will be flagged with the NHS Central Register to provide details of the date and cause of death. Discussion The Newcastle 85+ Study will address key questions about health and health-maintenance in the 85+ population, with a particular focus on quantitative assessment of factors underlying variability in health, and on the relationships between health, nutrition and biological markers of the fundamental processes of ageing.

Background Heart failure prevalence increases sharply at older ages. The section of the population aged 85 and over represents the most rapidly increasing demographic worldwide. Previous epidemiological studies of ventricular dysfunction and heart failure have included only small numbers of the “oldest old”, and have generally been conducted in hospital-based settings, potentially introducing ascertainment biases. We conducted a community-based study of the oldest old using domiciliary echocardiography to estimate the prevalence of cardiac dysfunction and heart failure. Since in elderly people with multiple comorbidities, heart failure may more frequently be incorrectly diagnosed, we cross-referenced our findings to preceding diagnoses present in general practice records. Methods Four hundred and twenty-seven individuals aged 86–89 years (mean age 87.9 years; 39.1% (n=167) men, 60.9% (n=260) women) were visited in their usual place of residence. A full cardiovascular and medical history, including current medication, was taken; symptoms were graded using the NYHA classification. Previous diagnoses of heart failure (HF) were abstracted from the GP record. Participants underwent 2-D and Doppler echocardiography, including tissue Doppler measurements of LV long axis velocities, using a portable instrument (Vivid-I, GE Healthcare). LV systolic and diastolic dysfunction were graded according to American Society of Echocardiography guidelines. Results LV systolic function could be quantified in 93.2% (n=398) participants and diastolic function (classified as normal, mild, moderate or severe dysfunction) in 88.1% (n=376). 37.2% of participants (n=140/376) had normal cardiac function or isolated mild diastolic dysfunction; 19.6% (n=78/398) had moderate or severe LV systolic dysfunction, which was commoner in men (27.4%) than women (14.5%); and 14.4% (n=54/376) had isolated moderate or severe diastolic dysfunction. 65.1% (278/427) of participants had valid data on previous diagnosis of HF, NYHA class and echocardiographic assessment of cardiac dysfunction. Of these, 37.4% (104/278) had clinical evidence of HF, which was defined as NYHA class II, III, or IV symptoms with underlying systolic dysfunction (29.5% (82/278)) or isolated moderate or severe diastolic dysfunction (7.9% (22/278)) on echo. Only 7.6% (21/278) had a previous diagnosis of HF. 33.1% (n=92/278) had no previous diagnosis of HF but had clinical evidence of HF and an additional 21.6% (n=60/278) had no previous diagnosis but evidence of pre-clinical HF (NYHA class I with systolic or moderate/severe diastolic dysfunction). Of those with a previous diagnosis of HF, 23.5% (n=5/21) had no echocardiographic evidence of cardiac dysfunction. Conclusions Systolic and diastolic dysfunction and HF were commoner in our population than previous studies in the “younger old” have suggested. There are significant levels of both undiagnosed and misdiagnosed HF in this age group.

Background Those aged 85 and over, the oldest old, are now the fastest growing sector of the population. Information on their health is essential to inform future planning; however, there is a paucity of up-to-date information on the oldest old, who are often excluded from research. The aim of the Newcastle 85+ Study is to investigate the health of a cohort of 85-year-olds from a biological, medical and psychosocial perspective. This paper describes the methods employed for the successful recruitment, retention and evaluation of this cohort. Methods Participants were all individuals born in 1921 and registered with a participating general practice in Newcastle and North Tyneside, UK. Involvement comprised detailed health assessments, by a nurse, in their usual place of residence and/or review of their general practice medical records. Results Of the 1453 individuals eligible to participate, 72% (n = 1042) were recruited; 59% (n = 851) consented to both health assessment and review of general practice records. Key factors for successful involvement included protected time to engage with family and other key gatekeepers, minimising participant burden, through for example home based assessment, and flexibility of approach. Cognitive impairment is a significant issue; due consideration should be given to the ethical and legal issues of capacity and consent. Interim withdrawal rates at phase 2 (18 month post baseline), show 88 out of 854 participants (10%) had withdrawn with approval for continued use of data and materials and a further 2 participants (0.2%) had withdrawn and requested that all data be destroyed. Attrition due to death of participants within this same time frame was 135 (16%). Conclusion Our recruitment rates were good and compared favourably with other similar UK and international longitudinal studies of the oldest old. The challenges of and successful strategies for involving, recruiting and retaining the oldest old in research, including those in institutions, are described to facilitate adequate representation of this growing population in future research into ageing.

Objectives The Newcastle 85+ Study aims to systematically study the clinical, biological, and psychosocial attributes of an unselected cohort of 85 year olds and to examine subsequent health trajectories as the cohort ages; health at baseline is reported. Design Cross sectional analysis of baseline data from a cohort study. Setting Newcastle upon Tyne and North Tyneside primary care trusts, United Kingdom. Participants 1042 people born in 1921 and registered with the participating general practices. Main outcome measures Detailed health assessment and review of general practice records (disease, medication, and use of general practice services); participants could decline elements of the protocol. Results Of the 1453 eligible people, 851 (58.6%) were recruited to health assessment plus record review, 188 (12.9%) to record review only, and 3 (0.2%) to health assessment only. Data from record review are reported on a maximum of 1030 and from health assessment on a maximum of 853; individual denominators differ owing to withdrawal and missing values. Of the health assessment sample (n=853), 62.1% (n=530) were women and 10.4% (n=89) were in institutional care. The most prevalent diseases were hypertension (57.5%, 592/1030) and osteoarthritis (51.8%, 534/1030). Moderate or severe cognitive impairment was present in 11.7% (96/824) of participants, severe or profound urinary incontinence in 21.3% (173/813), hearing impairment in 59.6% (505/848), and visual impairment in 37.2% (309/831). Health assessment identified participants with possible disease but without a previous diagnosis in their medical record for hypertension (25.1%, 206/821), ischaemic heart disease (12.6%, 99/788), depression (6.9%, 53/772), dementia (6.7%, 56/840), and atrial fibrillation (3.8%, 30/788). Undiagnosed diabetes mellitus and thyroid disease were rare (1%, 7/717 and 6/762, respectively). A median of 3 (interquartile range 1-8) activities of daily living were undertaken with difficulty. Overall, 77.6% (646/832) of participants rated their health compared with others of the same age as good, very good, or excellent. High contact rates in the previous year with general practitioners (93.8%, 960/1024) were recorded. Women had significantly higher disease counts (medians: women 5, men 4; P=0.033) and disability scores (medians: women 4, men 2; P=0.0006) than men, but were less likely to have attended outpatient clinics in the previous three months (women 29% (150/524), men 37% (118/320), odds ratio 0.7, 95% confidence interval 0.5 to 0.9). Conclusions This large cohort of 85 year olds showed good levels of both self rated health and functional ability despite significant levels of disease and impairment. Hypertension, ischaemic heart disease, atrial fibrillation, depression, and dementia may be underdiagnosed. Notable differences were found between the sexes: women outnumbered men and had more disease and disability.

Worldwide, the oldest old are the fastest growing section of the population yet there is little up-to-date information about their health or factors which maintain health and independence. The Newcastle 85+ Study is exploring the spectrum of health within an inception cohort of 85 year-olds and examining health trajectories and outcomes as the cohort ages. Health status at baseline will be presented. Members of the 1921 birth cohort were recruited from general practices in Newcastle and North Tyneside, …

Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown.Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N).Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models.Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) μg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort.There is an alarming high prevalence of vitamin D deficiency (30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

Inherited genetic variation of mitochondrial DNA (mtDNA) could account for the missing heritability of human longevity and healthy aging. Here, we show no robust association between common genetic variants of mtDNA and frailty (an “unhealthy aging” phenotype) or mortality in 700, more than 85-year-old, participants of the Newcastle 85+ study. Conflicting data from different populations underscore our conclusion that there is currently no compelling link between inherited mtDNA variants and aging.