Jane Fleming

Neuropathological Correlates of Dementia in Over-80-Year-Old Brain Donors from the Population-Based Cambridge City over-75s Cohort (CC75C) Study

Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimers Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimers disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimers disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age.

Prevalence studies of dementia in mainland china, Hong Kong and taiwan: a systematic review and meta-analysis.

Background Many studies have considered the prevalence of dementia in mainland China, Hong Kong and Taiwan. However, area level estimates have not been produced. This study examines area differences across mainland China, Hong Kong and Taiwan adjusting for the effect of methodological factors with the aim of producing estimates of the numbers of people with dementia in these areas. Method and Findings A search of Chinese and English databases identified 76 dementia prevalence studies based on samples drawn from mainland China, Hong Kong and Taiwan between 1980 and 2012. A pattern of significantly decreasing prevalence was observed from northern, central, southern areas of mainland China, Hong Kong and Taiwan. Area variations in dementia prevalence were not explained by differences in methodological factors (diagnostic criteria, age range, study sample size and sampling method), socioeconomic level or life expectancy between areas. The results of meta-analysis were applied to current population data to provide best estimate. Based on the DSM-IV diagnostic criteria, the total number of people aged 60 and over with dementia in mainland China, Hong Kong and Taiwan is 8.4 million (4.6%, 95% CI: 3.4, 5.8) and in northern, central and southern areas are 3.8 (5.1%, 95% CI: 4.1, 6.1), 3.2 (4.4%, 95% CI: 3.2, 5.6) and 1.2 (3.9%, 95% CI: 2.3, 5.4) million respectively. These estimates were mainly based on the studies existing in highly developed areas and potentially affected by incomplete and insufficient data. Conclusions The findings of this review provide a robust estimate of area differences in dementia prevalence. Application of the estimated prevalence to population data reveals the number of people with dementia is expected to double every 20 years, areas in mainland China will be facing the greatest dementia challenge.

Epidemiology of back pain in older adults: prevalence and risk factors for back pain onset

OBJECTIVES To determine the prevalence of disabling and non-disabling back pain across age in older adults, and identify risk factors for back pain onset in this age group. METHODS Participants aged ≥ 75 years answered interviewer-administered questions on back pain as part of a prospective cohort study [Cambridge City over-75s Cohort Study (CC75C)]. Descriptive analyses of data from two surveys, 1988-89 and 1992-93, estimated prevalence and new onset of back pain. Relative risks (RRs) and 95% CIs were estimated using Poisson regression, adjusted for age and gender. RESULTS Prevalence of disabling and non-disabling back pain was 6 and 23%, respectively. While prevalence of non-disabling back pain did not vary significantly across age (χ²trend : 0.90; P = 0.34), the prevalence of disabling back pain increased with age (χ²trend : 4.02; P = 0.04). New-onset disabling and non-disabling back pain at follow-up was 15 and 5%, respectively. Risk factors found to predict back pain onset at follow-up were: poor self-rated health (RR 3.8; 95% CI 1.8, 8.0); depressive symptoms (RR 2.2; 95% CI 1.3, 3.7); use of health or social services (RR 1.7; 95% CI 1.1, 2.7); and previous back pain (RR 2.1; 95% CI 1.2-3.5). From these, poor self-rated health, previous back pain and depressive symptoms were found to be independent predictors of pain onset. Markers of social networks were not associated with the reporting of back pain onset. Conclusion. The risk of disabling back pain rises in older age. Older adults with poor self-rated health, depressive symptoms, increased use of health and social services and a previous episode of back pain are at greater risk of reporting future back pain onset.

Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies

Importance Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. Objective To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Design, Setting, and Participants Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Exposures Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Outcomes Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. Results There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (−2.8 points; 95% CI, −4.5 to −1.0; P < .001). Cognitive decline attributable to delirium was −0.37 MMSE points per year (95% CI, −0.60 to −0.13; P < .001). Decline attributable to the pathologic processes of dementia was −0.39 MMSE points per year (95% CI, −0.57 to −0.22; P < .001). However, the combination of delirium and the pathologic processes of dementia resulted in the greatest decline, in which the interaction contributed an additional −0.16 MMSE points per year (95% CI, −0.29 to −0.03; P = .01). The multiplicative nature of these variables resulted in individuals with delirium and the pathologic processes of dementia declining 0.72 MMSE points per year faster than age-, sex-, and educational level–matched controls. Conclusions and Relevance Delirium in the presence of the pathologic processes of dementia is associated with accelerated cognitive decline beyond that expected for delirium or the pathologic process itself. These findings suggest that additional unmeasured pathologic processes specifically relate to delirium. Age-related cognitive decline has many contributors, and these findings at the population level support a role for delirium acting independently and multiplicatively to the pathologic processes of classic dementia.

The oldest old in the last year of life: population-based findings from Cambridge city over-75s cohort study participants aged 85 and older at death.

OBJECTIVES: To characterize people of advanced old age in their last year of life and compare those dying in their late 80s with those dying aged 90 and older to inform policy and planning.

Place of death and end-of-life transitions experienced by very old people with differing cognitive status: Retrospective analysis of a prospective population-based cohort aged 85 and over

Background: Despite fast-growing ‘older old’ populations, ‘place of care’ trajectories for very old people approaching death with or without dementia are poorly described and understood. Aim: To explore end-of-life transitions of ‘older old’ people across the cognitive spectrum. Design: Population-based prospective cohort (United Kingdom) followed to death. Setting/participants: Mortality records linked to 283 Cambridge City over-75s Cohort participants’ cognitive assessments <1 year before dying aged ≥85 years. Results: Overall, 69% were community dwelling in the year before death; of those with severe cognitive impairment 39% were community dwelling. Only 6% subsequently changed their usual address. However, for 55% their usual address on death registration was not their place of death. Dying away from the ‘usual address’ was associated with cognition, overall fewer moving with increasing cognitive impairment – cognition intact 66%, mildly/moderately impaired 55% and severely impaired 42%, trend p = 0.003. This finding reflects transitions being far more common from the community than from institutions: 73% from the community and 28% from institutions did not die where last interviewed (p < 0.001). However, severely cognitively impaired people living in the community were the most likely group of all to move: 80% (68%−93%). Hospitals were the most common place of death except for the most cognitively impaired, who mostly died in care homes. Conclusion: Most very old community-dwelling individuals, especially the severely cognitively impaired, died away from home. Findings also suggest that long-term care may play a role in avoidance of end-of-life hospital admissions. These results provide important information for planning end-of-life services for older people across the cognitive spectrum, with implications for policies aimed at supporting home deaths. MeSH Terms: Cognitive impairment, Dementia, Aged, 80 and over, Aged, frail elderly, Patient Transfer, Residential characteristics, Homes for the aged, Nursing Homes, Delivery of Health Care, Terminal care Other key phrases: Older old, Oldest old, Place of death, Place of care, End-of-life care.

Period, birth cohort and prevalence of dementia in mainland China, Hong Kong and Taiwan: a meta-analysis

There have been dramatic societal changes in East Asia over the last hundred years. Several of the established risk factors could have important period and cohort effects. This study explores temporal variation of dementia prevalence in mainland China, Hong Kong and Taiwan taking study methods into account.

Place of death for the ‘oldest old’: ≥85-year-olds in the CC75C population-based cohort

BACKGROUND Deaths are rising fastest among the oldest old but data on their transitions in place of care at the end of life are scarce. AIM To examine the place of residence or care of > or =85 year-olds less than a year before death, and their place of death, and to map individual changes between the two. DESIGN OF STUDY Population-based cohort study. SETTING Cambridge City over-75s Cohort (CC75C) study, UK. METHOD Retrospective analysis of prospective data from males and females aged > or =85 years at death who died within a year of taking part in any CC75C survey (n = 320); death certificate linkage. RESULTS Only 7% changed their address in their last year of life, yet 52% died somewhere other than their usual address at the time of death. Over two-thirds were living in the community when interviewed <1 year before death, but less than one-third who had lived at home died there (less than one-fifth in sheltered housing). Care homes were the usual address of most people dying there (77% in residential homes, 87% in nursing homes) but 15% of deaths in acute hospital came from care homes. CONCLUSION More than half the study sample of individuals of advanced old age had a change in their place of residence or care in their last year of life. These findings add weight to calls for improved end-of-life care in all settings, regardless of age, to avoid unnecessary transfers. The study data provide a baseline that can help plan and monitor initiatives to promote choice in location of care at the end of life for the very old.

Death and the Oldest Old: Attitudes and Preferences for End-of-Life Care--Qualitative Research within a Population-Based Cohort Study.

Introduction Increasing longevity means more people will be dying in very old age, but little is known about the preferences of the ‘oldest old’ regarding their care at the end of life. Aims To understand very old people’s preferences regarding care towards the end of life and attitudes towards dying, to inform policy and practice. Methods Qualitative data collection for n = 42 population-based cohort study participants aged 95–101 (88% women, 42% in long-term-care): topic-guided interviews with n = 33 participants and n = 39 proxy informants, most with both (n = 30: 4 jointly + separate interviews for 26 dyads). Results Death was a part of life: these very old people mainly live day-to-day. Most were ready to die, reflecting their concerns regarding quality of life, being a nuisance, having nothing to live for and having lived long enough. Contrasting views were rare exceptions but voiced firmly. Most were not worried about death itself, but concerned more about the dying process and impacts on those left behind; a peaceful and pain-free death was a common ideal. Attitudes ranged from not wanting to think about death, through accepting its inevitable approach to longing for its release. Preferring to be made comfortable rather than have life-saving treatment if seriously ill, and wishing to avoid hospital, were commonly expressed views. There was little or no future planning, some consciously choosing not to. Uncertainty hampered end-of-life planning even when death was expected soon. Some stressed circumstances, such as severe dependency and others’ likely decision-making roles, would influence choices. Carers found these issues harder to raise but felt they would know their older relatives’ preferences, usually palliative care, although we found two discrepant views. Conclusions This study’s rare data show ≥95-year-olds are willing to discuss dying and end-of-life care but seldom do. Formal documentation of wishes is extremely rare and may not be welcome. Although being “ready to die” and preferring a palliative approach predominated, these preferences cannot be assumed.

The relationship between back pain and mortality in older adults varies with disability and gender: Results from the Cambridge City over-75s Cohort (CC75C) study

This study aims to determine whether older adults reporting back pain (BP) are at increased risk of premature mortality, specifically, to examine the association with disabling/non‐disabling pain separately.