The frequency and validity of self-reported diagnosis of Parkinson's Disease in the UK elderly: MRC CFAS cohort

Background: Estimates of the incidence and prevalence of chronic diseases can be made using established cohort studies but these estimates may have lower reliability if based purely on self-reported diagnosis.Methods: The MRC Cognitive Function & Ageing Study ( MRC CFAS) has collected longitudinal data from a population-based random sample of 13004 individuals over the age of 65 years from 5 centres within the UK. Participants were asked at baseline and after a two-year follow-up whether they had received a diagnosis of Parkinson's disease. Our aim was to make estimates of the incidence and prevalence of PD using self-reporting, and then investigate the validity of self-reported diagnosis using other data sources where available, namely death certification and neuropathological examination.Results: The self-reported prevalence of Parkinson's disease ( PD) amongst these individuals increases with age from 0.7% (95% CI 0.5 - 0.9) for 65 - 75, 1.4% ( 95% CI 1.0 - 1.7) for 75 - 85, and 1.6% ( 95% CI 1.0 - 2.3) for 85+ age groups respectively. The overall incidence of self reported PD in this cohort was 200/100,000 per year ( 95% CI 144 - 278). Only 40% of the deceased individuals reporting prevalent PD and 35% of those reporting incident PD had diagnoses of PD recorded on their death certificates. Neuropathological examination of individuals reporting PD also showed typical PD changes in only 40%, with the remainder showing basal ganglia pathologies causing parkinsonism rather than true PD pathology.Conclusion: Self-reporting of PD status may be used as a screening tool to identify patients for epidemiological study, but inevitably identifies a heterogeneous group of movement disorders patients. Within this group, age, male sex, a family history of PD and reduced cigarette smoking appear to act as independent risk factors for self-reported PD

Lewy bodies and neuronal loss in subcortical areas and disability in non-demented older people: a population based neuropathological cohort study.

BACKGROUND: Functional disability, the loss of ability to carry out daily tasks unaided, is a major adverse outcome more common with increasing age. The potential contribution of neuropathological changes in subcortical areas of the brain associated with normal ageing may be a contributing factor to this loss of function. This study investigates the clinicopathological relationship between functional ability during life and pathological correlates identified at post mortem in an UK population of older people (66-102 years).The aim is to examine the clinicopathological correlates of functional disability in subcortical neuronal populations of non-demented elderly individuals. METHODS: 156 non-demented participants in the brain donation programme of the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) were included in this study. Neuropathological examination was based on the CERAD protocol; pathologies of interest were amyloid plaques, neurofibrillary tangles, Lewy bodies, vascular disease and neuronal loss. Self-reported functional ability was scored according to a combined activities of daily living and instrumental activities of daily living scale. RESULTS: Functional disability was equally common in men and women over 65 years, and in both sexes disability was more common at older ages. Neuronal loss in several subcortical regions elevated the risk of functional disability by three-fold (95% CI 1.3-6.6). There was evidence for a relationship between Lewy bodies in the SN and functional disability. CONCLUSION: Neuronal loss in subcortical regions is associated with functional disability in the older population. The causal relationships are not defined and require further investigation

An investigation of the population impact of variation in HbA1c levels in older people in England and Wales: from a population based multi-centre longitudinal study.

BACKGROUND: Diabetes is common in the older population and is increasing. Glycated hemoglobin (HbA1c) is an indicator of average blood glucose concentration over the past three months. The HbA1c test is currently one of clinical methods used to check diabetes control. Recent studies have suggested diabetes is a risk factor for dementia, cognitive dysfunction and physical disability. In addition, there have reported the relationship between HbA1c and mortality on all cause, cardiovascular disease and cognitive function, but few studies have investigated the relationship concentrating on the older population. The aim of this study is to investigate the association between the level of HbA1c and mortality from all causes, incident cardiovascular disease, cognitive decline and physical disability in people aged 65 and over in England and Wales. METHODS: 1139 men and women aged 69 years and over who were participants in a ten year population based ageing multi-centre, longitudinal study who had HbA1c measurements after 5-6 years of follow up. All participants were flagged for death notification including causes at the Office of National Statistics. Information on health including vascular conditions, cognitive status, physical function and dementia were available from the study both before and after the HbA1c measurement. Survival analyses and logistic regression were conducted. RESULTS: Mortality from all causes, cardiovascular and ischaemic heart disease increased with increasing HbA1c. Participants with diagnosed diabetes or who had HbA1c > or = 7% but no self-reported diabetes had increased mortality risk from all causes and cardiovascular diseases. The respondents in the group HbA1c > or = 7% who had not been diagnosed with diabetes had a significantly higher risk (odds ratio = 4.8 95% CI: 1.1 to 21.6) of developing dementia. Individuals who had self-reported diabetes but a HbA1c level < 7% had mortality and dementia incidence comparable to individuals without diabetes and HbA1c < 7%. CONCLUSION: The findings support previous reports that bio-markers of glucose metabolism are associated with long term outcomes, such as mortality and dementia

Regional differences in multidimensional aspects of health: findings from the MRC cognitive function and ageing study.

BACKGROUND: Differences in mortality and health experience across regions are well recognised and UK government policy aims to address this inequality. Methods combining life expectancy and health have concentrated on specific areas, such as self-perceived health and dementia. Few have looked within country or across different areas of health. Self-perceived health, self-perceived functional impairment and cognitive impairment are linked closely to survival, as well as quality of life. This paper aims to describe regional differences in healthy life expectancy using a variety of states of health and wellbeing within the MRC Cognitive Function and Ageing Study (MRC CFAS). METHODS: MRC CFAS is a population based study of health in 13,009 individuals aged 65 years and above in five centres using identical study methodology. The interviews included self-perceived health and measures of functional and cognitive impairment. Sullivan's method was used to combine prevalence rates for cognitive and functional impairment and life expectancy to produce expectation of life in various health states. RESULTS: The prevalence of both cognitive and functional impairment increases with age and was higher in women than men, with marked centre variation in functional impairment (Newcastle and Gwynedd highest impairment). Newcastle had the shortest life expectancy of all the sites, Cambridgeshire and Oxford the longest. Centre differences in self-perceived health tended to mimic differences in life expectancy but this did not hold for cognitive or functional impairment. CONCLUSION: Self-perceived health does not show marked variation with age or sex, but does across centre even after adjustment for impairment burden. There is considerable centre variation in self-reported functional impairment but not cognitive impairment. Only variation in self-perceived health relates to the ranking of life expectancy. These data confirm that quite considerable differences in life experience exist across regions of the UK beyond basic life expectancy.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Cohort differences in disease and disability in the young-old: findings from the MRC Cognitive Function and Ageing Study (MRC-CFAS).

BACKGROUND: Projections of health and social care need are highly sensitive to assumptions about cohort trends in health and disability. We use a repeated population-based cross-sectional study from the Cambridgeshire centre of the UK Medical Research Council Cognitive Function and Ageing Study to investigate trends in the health of the young-old UK population METHODS: Non-overlapping cohorts of men and women aged 65-69 years in 1991/2 (n = 689) and 1996/7 (n = 687) were compared on: self-reported diseases and conditions; self-rated health; mobility limitation; disability by logistic regression and four-year survival by Cox Proportional Hazards Regression models, with adjustments for differences in socio-economic and lifestyle factors. RESULTS: Survival was similar between cohorts (HR: 0.91, 95% CI: 0.62 to 1.32). There was a significant increase in the number of conditions reported between cohorts, with more participants reporting 3 or more conditions in the new cohort (14.2% vs. 10.1%). When individual conditions were considered, there was a 10% increase in the reporting of arthritis and a significant increase in the reporting of chronic airways obstruction (OR: 1.36, 95% CI: 1.04 to 1.78). CONCLUSION: This study provides evidence of rising levels of ill-health, as measured by the prevalence of self-reported chronic conditions, in the newer cohorts of the young-old. Though changes in diagnosis or reporting of disease cannot, as yet, be excluded, to better understand whether our findings reflect real increases in ill-health, investment should be made into improved population-based databases, linking self-report and objective measures of health and function, and including those in long-term care

An evaluation of the psychometric properties of the Indicator of Relative Need (IoRN) instrument

BACKGROUND: The Indicator of Relative Need (IoRN) instrument is designed for both health and social care services to measure function and dependency in older people. To date, the tool has not undergone assessment of validity. We report two studies aimed to evaluate psychometric properties of the IoRN. METHODS: The first study recruited patients receiving social care at discharge from hospital, those rehabilitating in intermediate care, and those in a rehabilitation at home service. Participants were assessed using the IoRN by a single researcher and by the clinical team at baseline and 8 weeks. Comparator instruments (Barthel ADL, Nottingham Extended ADL and Townsend Disability Scale) were also administered. Overall change in ability was assessed with a 7 point Likert scale at 8 weeks. The second study analysed linked routinely collected, health and social care data (including IoRN scores) to assess the relationship between IoRN category and death, hospitalisation and care home admission as a test of external validity. RESULTS: Ninety participants were included in the first study, mean age 77.9 (SD 12.0). Cronbach’s alpha for IoRN subscales was high (0.87 to 0.93); subscales showed moderate correlation with comparator tools (r = 0.43 to 0.63). Cohen’s weighted kappa showed moderate agreement between researcher and clinician IoRN category (0.49 to 0.53). Two-way intraclass correlation coefficients for IoRN subscales in participants reporting no change in ability were high (0.88 to 0.98) suggesting good stability; responsiveness coefficients in participants reporting overall change were equal to or better than comparator tools. 1712 patients were included in the second study, mean age 81.0 years (SD 7.7). Adjusted hazard ratios for death, care home admission and hospitalisation in the most dependent category compared to the least dependent IoRN category were 5.9 (95 % CI 2.0–17.0); 7.2 (95 % CI 4.4–12.0); 1.1 (95 % CI 0.5–2.6) respectively. The mean number of allocated hours of care 6 months after assessment was higher in the most dependent group compared to the least dependent group (5.6 vs 1.4 h, p = 0.005). CONCLUSIONS: Findings from these analyses support the use of the IoRN across a range of clinical environments although some limitations are highlighted

Subjective memory complaints, mood and MCI: a follow-up study

Objectives: Subjective memory complaints (SMC) are common in older people and previous research has shown an association with mood problems, such as depression and anxiety. SMC form part of the criteria for many definitions of mild cognitive impairment (MCI), but there is controversy over whether they should be included as they may be related more strongly to mood than to objective cognitive impairment. This study aims to clarify the relationship between mood and SMC in people with MCI. Method: This paper reports an analysis of data from the Medical Research Council Cognitive Function and Ageing study. Structured interviews were conducted with community-dwelling older people to assess a range of aspects of cognitive functioning and mood. Data from two time points approximately 24 months apart were used in this analysis. At baseline, participants without dementia or severe cognitive impairment were categorised into three groups according to cognitive status. Mood was investigated by assessing symptoms of anxiety and depression which were defined using a diagnostic algorithm. Associations were tested using logistic regression and chi square analyses. Results: A clear association was shown between SMC and mood, both cross-sectionally and over time. The relationship between our two competing definitions of MCI suggested that mood problems were more strongly related to the presence of SMC than objective cognitive impairment. Conclusion: SMC may be a function of anxiety and depression rather than being related to objective cognitive function. This questions whether SMC should be included in definitions of MCI

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined

TREM2 Expression in the Human Brain: A Marker of Monocyte Recruitment

Abstract Mutation in the triggering receptor expressed on myeloid cells (TREM) 2 gene has been identified as a risk factor for several neurodegenerative diseases including Alzheimer’s disease (AD). Experimental studies using animal models of AD have highlighted a number of functions associated with TREM2 and its expression by microglial cells. It has therefore been assumed that this is also the case in humans. However, there is very limited information concerning the cellular expression of TREM2 in the human brain. As part of investigations of microglia using post-mortem resources provided by the Medical Research Council Cognitive Function and Ageing Studies (MRC-CFAS), we immunostained the cerebral cortex of 299 participants for TREM2 using the Sigma antibody HPA010917 and compared with the macrophage/microglial markers Iba1 and CD68. As expected, Iba1 and CD68 labelled microglia and perivascular macrophages. However, in most cases (284/299), the TREM2 antibody labelled monocytes within vascular lumens, but not microglia or perivascular macrophages. In contrast, in 5 out of 6 cases with acute infarcts, TREM2 immunoreaction identified cells within the brain parenchyma interpreted as recruited monocytes. Six cases with old infarcts contained phagocytic foamy macrophages which were CD68-positive but TREM2 negative. Our observations, using the HPA010917 anti-TREM2 antibody, suggest that TREM2 is not expressed by microglia but instead seems to be a marker of recruited monocytes in the human brain. This finding has implications with regards to the role of TREM2 as a risk factor, emphasizing the importance of systemic immune responses in the development and progression of Alzheimer’s disease.The study was supported in part by: a Special Project grant and a Programme grant from the MRC and the Department of Health; the UK NIHR Biomedical Research Centre for Ageing and Age—related Disease Award to the Newcastle-upon-Tyne Hospitals Foundation Trust; the Cambridge Brain Bank is supported by the NIHR Cambridge Biomedical Research Centre; The Cambridgeshire and Peterborough NIHR CLAHRC; Nottingham University Hospitals NHS Trust; University of Sheffield and the Sheffield Teaching Hospitals NHS Foundation Trust; The Thomas Willis Oxford Brain Collection, supported by the Oxford Biomedical Research Centre; The Walton Centre NHS Foundation Trust, Liverpool