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

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

Older people, the natural environment and common mental disorders: cross-sectional results from the Cognitive Function and Ageing Study.

OBJECTIVES: To explore the hypothesis that higher exposure to natural environments in local areas is associated with a lower odds of depression and anxiety in later life. DESIGN: A cross-sectional study based on the year-10 interview of the Medical Research Council Cognitive Function and Ageing Study (CFAS), a population-based study of ageing in the UK. Postcodes of the CFAS participants were mapped onto small geographic units, lower-layer super output areas (LSOAs) and linked to environmental data from government databases. The natural environment was characterised as the percentage of green space and private gardens in each LSOA based on the UK Generalised Land Use 2001 Dataset. PARTICIPANTS: 2424 people aged 74 and over in the CFAS year-10 follow-up interview (2001) from 4 English centres (Cambridgeshire, Nottingham, Newcastle and Oxford). MAIN OUTCOME MEASURES: Depression and anxiety; clinical and subthreshold cases were identified using the Geriatric Mental State Examination (GMS) package and its associated diagnostic algorithm: the Automated Geriatric Examination for Computer Assisted Taxonomy. RESULTS: Compared with the lowest quartile, living in the highest quartile of neighbourhood natural environment provision was associated with a reduced odds of subthreshold depression (OR 0.66, 95% CI 0.46 to 0.95), anxiety symptoms (OR 0.62, 95% CI 0.46 to 0.83) and their co-occurrence (OR 0.55, 95% CI 0.35 to 0.84) after adjusting for individual-level factors. Controlling for area deprivation attenuated the strength of associations for subthreshold depression by 20% but not for anxiety symptoms or for co-occurrence of the conditions. CONCLUSIONS: A high exposure to natural environments (green space and gardens) in communities was associated with fewer mental disorders among older people. Increasing provision of green environments in local areas could be a potential population-level intervention to improve mental health among older people.The Cognitive Function and Ageing Studies (CFAS) were funded by the Department of Health and the Medical Research Council [grant number G9901400]. Yu-Tzu Wu received a PhD scholarship from the Cambridge Trust, University of Cambridge. Fiona E. Matthews and A. Matthew Prina were supported by the Medical Research Council [grant number U105292687 and MR/K021907/1].This is the final version of the article. It first appeared from BMJ via http://dx.doi.org/10.1136/bmjopen-2015-00793

Relocation at older age: results from the Cognitive Function and Ageing Study.

BACKGROUND: Community environment might play an important role in supporting ageing in place. This paper aims to explore relocation at older age and its associations with individual and community level factors. METHODS: The postcodes of the 2424 people in the year-10 interview of the Cognitive Function and Ageing Study (CFAS) in England were mapped onto Enumeration Districts and linked to their corresponding Townsend deprivation score and the 2011 rural/urban categories. Multilevel logistic regression was conducted to examine the influence of the baseline individual (age, gender, education and social class) and community (rural/urban categories and area deprivation) level factors on relocation over 10 years. RESULTS: One-third of people moved residence after the age of 65 years and over. Older age, low education, low social class and living in rural areas at baseline were associated with higher probability of moving later in life. The likelihood of relocation in later life increased from least to most deprived areas (odds ratio: 2.0, 95% confidence interval: 1.4, 2.8). CONCLUSIONS: Urban/rural contexts and area deprivation are associated with relocation at older age and indicate that community environment may be relevant to ageing in place.Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) was funded by the Department of health and the Medical Research Council (grant number G9901400); F.E.M. and A.M.P. are supported by the Medical Research Council (grant number U105292687 and MR/K021907/1); Y.-T.W. received a PhD scholarship from Cambridge Trust, University of Cambridge. We thank the participants, their families, general practitioners and their staff, and the primary care trusts for their cooperation and support.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/pubmed/fdv05

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

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

Land use mix and five-year mortality in later life: Results from the Cognitive Function and Ageing Study.

This study explores the potential modifying effect of age and mediation effect of co-morbidity on the association between land use mix, a measure of neighbourhood walkability, and five-year mortality among the 2424 individuals participating in the year-10 follow-up of the Cognitive Function and Ageing Study in England. Postcodes of participants were mapped onto Lower-layer Super Output Areas, a small area level geographical unit in the UK, and linked to Generalised Land Use data. Cox regression models were fitted to investigate the association. For the younger older age group (75-79 years), the effect of high land use mix on an elevated risk of mortality was mediated by co-morbidity. For older old age groups (80-84, 85+ years), a higher land use mix was directly associated with a 10% lower risk of five-year mortality. The findings suggest differential impacts of land use mix on the health of the younger and older old.Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) was funded by the Department of Health and the Medical Research Council, [Grant number G9901400]; Fiona E Matthews and Matthew Prina are supported by the Medical Research Council [Grant number U105292687 & MR/K021907/1]; Yu-Tzu Wu received a PhD scholarship from Cambridge Trust, University of Cambridge. We thank the participants, their families, general practitioners and their staff, and the primary care trusts for their cooperation and support.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.healthplace.2015.12.00

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

Micro-scale environment and mental health in later life: Results from the Cognitive Function and Ageing Study II (CFAS II)

$\textit{Background:}$ Poor micro-scale environmental features, such as graffiti and broken windows, have been associated with crime and signs of social disorder with a potential impact on mental health. The aim of this study is to investigate the association between micro-scale environment and mental health problems in later life, including cognitive (cognitive impairment and dementia) and common mental disorders (depressive and anxiety symptoms). $\textit{Methods:}$ The method of visual image audits was used to collect micro-scale environmental data for 3590 participants in the Cognitive Function and Ageing Study II, a population-based multicentre cohort of people aged 65 or above in England. Multilevel logistic regression was used to examine the associations between the quality of micro-scale environment and mental health problems taking into account urban/rural difference. $\textit{Results:}$ Poor quality of micro-scale environment was associated with nearly 20% increased odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17; 95% CI: 0.99, 1.38) while the direction of association for cognitive disorders differed across urban and rural settings. Although higher odds of cognitive disorders were found in rural settings, living in a poor quality environment was associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95% CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR: 0.80; 95% CI: 0.57, 1.11). $\textit{Limitations:}$ The causal direction could not be fully determined due to the cross-sectional nature of the data. The visual nature of the environmental assessment tool means it likely does not fully capture features related to the availability of local support services, or opportunities for social participation and interaction. $\textit{Conclusions:}$ The quality of micro-scale environment appears to be important to mental health in older people. Interventions may incorporate the environmental aspect to reduce cognitive and common mental disorders.Medical Research Counci

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