Longitudinal changes in global and domain specific cognitive function in the very-old: findings from the Newcastle 85+ Study.

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.

Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age.

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 (<65 years) followed by replication in an additional set of 13 060 long-lived individuals and 61 156 controls. In addition, we performed a subset analysis in cases aged ≥ 90 years. We observed genome-wide significant association with longevity, as reflected by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P = 1.74 × 10(-8)). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 × 10(-36)), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34 103), the minor allele of rs2149954 (T) on chromosome 5q33.3 associates with increased survival (HR = 0.95, P = 0.003). This allele has previously been reported to associate with low blood pressure in middle age. Interestingly, the minor allele (T) associates with decreased cardiovascular mortality risk, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less dependent on blood pressure. Hence, the pleiotropic mechanisms by which this intragenic variation contributes to lifespan regulation have to be elucidated.

Respiratory health and disease in a U.K. population-based cohort of 85†year olds: The Newcastle 85+ Study.

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.

Micronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study.

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 % (n 756) 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 (n 175), K (n 238) and Se (n 418) (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.

Macronutrient intake and food sources in the very old: analysis of the Newcastle 85+ Study.

Food and nutrient intake data are scarce in very old adults (85 years and older) - one of the fastest growing age segments of Western societies, including the UK. Our primary objective was to assess energy and macronutrient intakes and respective food sources in 793 85-year-olds (302 men and 491 women) living in North-East England and participating in the Newcastle 85+ cohort Study. Dietary information was collected using a repeated multiple-pass recall (2×24 h recalls). Energy, macronutrient and NSP intakes were estimated, and the contribution (%) of food groups to nutrient intake was calculated. The median energy intake was 6·65 (interquartile ranges (IQR) 5·49-8·16) MJ/d - 46·8 % was from carbohydrates, 36·8 % from fats and 15·7 % from proteins. NSP intake was 10·2 g/d (IQR 7·3-13·7). NSP intake was higher in non-institutionalised, more educated, from higher social class and more physically active 85-year-olds. Cereals and cereal products were the top contributors to intakes of energy and most macronutrients (carbohydrates, non-milk extrinsic sugars, NSP and fat), followed by meat and meat products. The median intakes of energy and NSP were much lower than the estimated average requirement for energy (9·6 MJ/d for men and 7·7 MJ/d for women) and the dietary reference value (DRV) for NSP (≥18 g/d). The median SFA intake was higher than the DRV (≤11 % of dietary energy). This study highlights the paucity of data on dietary intake and the uncertainties about DRV for this age group.

Age-related frailty and its association with biological markers of ageing.

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 <0.12. Higher values of each FI were associated with higher mortality risk. In a sex-adjusted model, each one percent increase in the FI-B increased the hazard ratio by 5.4 % (HR, 1.05; CI, 1.04-1.06). The FI-B was more powerful for mortality prediction than any individual biomarker and was robust to biomarker substitution. The ROC analysis showed moderate discriminative ability for 7-year mortality (AUC for FI-CD = 0.71 and AUC for FI-B = 0.66). No individual biomarker's AUC exceeded 0.61. The AUC for combined FI-CD/FI-B was 0.75. CONCLUSIONS: Many biological processes are implicated in ageing. The systemic effects of these processes can be elucidated using the frailty index approach, which showed here that subclinical deficits increased the risk of death. In the future, blood biomarkers may indicate the nature of the underlying causal deficits leading to age-related frailty, thereby helping to expose targets for early preventative interventions.

A comparison of subjective and objective measures of physical activity from the Newcastle 85+ study.

BACKGROUND: Little is known about physical activity (PA) in the very old, the fastest growing age group in the population. We aimed to examine the convergent validity of subjective and objective measures of PA in adults aged over 85 years. METHODS: A total of 484 participants aged 87-89 years recruited to the Newcastle 85+ study completed a purpose-designed physical activity questionnaire (PAQ), which categorised participants as mildly active, moderately active and very active. Out of them, 337 participants wore a triaxial, raw accelerometer on the right wrist over a 5-7-day period to obtain objective measures of rest/activity, PA intensity and PA type. Data from subjective and objective measurement methods were compared. RESULTS: Self-reported PA was significantly associated with objective measures of the daily sedentary time, low-intensity PA and activity type classified as sedentary, activities of daily living and walking. Objective measures of PA were significantly different when low, moderate and high self-reported PA categories were compared (all P < 0.001). CONCLUSION: The Newcastle 85+ PAQ demonstrated convergent validity with objective measures of PA. Our findings suggest that this PAQ can be used in the very old to rank individuals according to their level of total PA.

Acquisition of aberrant DNA methylation is associated with frailty in the very old: findings from the Newcastle 85+ Study.

Frailty is a major health problem in older people and, as the population ages, identification of its underlying biological mechanisms will be increasingly important. DNA methylation patterns within genomic DNA change during ageing and alterations in DNA methylation, particularly at gene promoter regions, can lead to altered gene expression. However the importance of altered DNA methylation in frailty is largely unknown. Using cross-sectional data from the Newcastle 85+ Study (all participants aged 85 years) frailty was operationalized by the Fried model. DNA methylation levels were assessed by highly quantitative pyrosequencing at the gene promoter associated CpG islands from a panel of five age-related methylation marker loci and at LINE-1 repetitive elements (as a surrogate for genome-wide methylation). While genome-wide methylation (as assessed at LINE-1 elements) showed no association with frailty status, there was a clear association between CpG island methylation and frailty. When compared to participants with CpG island methylation levels in the combined middle two (referent) quartiles, those in the lowest quartile had significantly decreased odds of frailty [odds ratio 0.47 (95 % CI 0.26-0.85); n = 321, p = 0.013]. Overall this study suggests a potential role for age-related changes in CpG island methylation in the development of frailty.

Utility of NT-proBNP as a rule-out test for left ventricular dysfunction in very old people with limiting dyspnoea: the Newcastle 85+ Study.

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. 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 (125 ng/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 (400 ng/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.

Assessment of sleep and circadian rhythm disorders in the very old: the Newcastle 85+ Cohort Study.

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.

The impact of visual impairment on Mini-Mental State Examination Scores in the Newcastle 85+ study.

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<0.001 for each) but also for some subscale scores not obviously requiring vision: orientation (P=0.018) and repetition (P=0.030). Excluding visual items, there was no significant difference in MMSE scores between those with/without SI. CONCLUSION: SI may be an obstacle to older people completing cognitive assessments including tasks requiring vision. People with SI also scored lower on some tasks not obviously requiring vision. An association between cognitive impairment and SI may exist beyond simply being unable to see the test material in cognitive tests.

Capability and dependency in the Newcastle 85+ cohort study. Projections of future 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.

Engaging the oldest old in research: lessons from the Newcastle 85+ study.

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.

CMV-independent increase in CD27-CD28+ CD8+ EMRA T cells is inversely related to mortality in octogenarians.

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.

A meta-analysis of genome-wide association studies identifies multiple longevity genes.

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.

A comparison of computerized and pencil-and-paper tasks in assessing cognitive function in community-dwelling older people in the Newcastle 85+ Pilot Study.

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.

The Newcastle 85+ study: biological, clinical and psychosocial factors associated with healthy ageing: study protocol.

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.

Deconstructing Complex Multimorbidity in the Very Old: Findings from the Newcastle 85+ Study.

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.

Serum Thyroid Function, Mortality and Disability in Advanced Old Age: The Newcastle 85+ Study.

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.