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Biomedical subjects

C Brayne

Publications and source records attributed to C Brayne.

At least 37 records · Page 2Linked to original sources
PubMed2000

Population norms for the MMSE in the very old: estimates based on longitudinal data. Mini-Mental State Examination.

OBJECTIVE: To report the percentile distribution of Mini-Mental State Examination (MMSE) scores in older people by age, sex, and education level, estimated from longitudinal data, after correcting for loss due to dropout. METHODS: The Cambridge City over 75 Cohort is a population-based study of a cohort of 2106 subjects age 75 years and older at study entry followed up over 9 years. At each of the four waves, cognitive function was assessed using MMSE. Based on these data, the relationship between age and MMSE score was modeled. Percentile distributions by age, sex, and education level were provided using inverse probability weighting to correct for dropouts. RESULTS: Performance on MMSE was related to age in men and women. In women, at age 75, MMSE score ranged from 21 (10th percentile) to 29 (90th percentile). At age 95, the range was 10 (10th percentile) to 27 (90th percentile). The upper end of MMSE distribution was slightly modified with age, whereas the lower end of the distribution was very sensitive to age effect. A similar pattern was observed in both sexes. CONCLUSION: These findings provide norms for MMSE scores in subjects age 75 years and older from longitudinal population-based data. Such norms can be used as reference values to determine where an individual's score lies in relation to his or her age, sex, and education level.

Aged↗
PubMed2000

Education and the risk for Alzheimer's disease: sex makes a difference. EURODEM pooled analyses. EURODEM Incidence Research Group.

The hypothesis that a low educational level increases the risk for Alzheimer's disease remains controversial. The authors studied the association of years of schooling with the risk for incident dementia and Alzheimer's disease by using pooled data from four European population-based follow-up studies. Dementia cases were identified in a two-stage procedure that included a detailed diagnostic assessment of screen-positive subjects. Dementia and Alzheimer's disease were diagnosed by using international research criteria. Educational level was categorized by years of schooling as low (< or =7), middle (8-11), or high (> or =12). Relative risks (95% confidence intervals) were estimated by using Poisson regression, adjusting for age, sex, study center, smoking status, and self-reported myocardial infarction and stroke. There were 493 (328) incident cases of dementia (Alzheimer's disease) and 28,061 (27,839) person-years of follow-up. Compared with women with a high level of education, those with low and middle levels of education had 4.3 (95% confidence interval: 1.5, 11.9) and 2.6 (95% confidence interval: 1.0, 7.1) times increased risks, respectively, for Alzheimer's disease. The risk estimates for men were close to 1.0. Finding an association of education with Alzheimer's disease for women only raises the possibility that unmeasured confounding explains the previously reported increased risk for Alzheimer's disease for persons with low levels of education.

Age Distribution↗
PubMed2000

Cognitive function in UK community-dwelling African Caribbean and white elders: a pilot study.

In recent years there has been interest in risk of cognitive impairment and dementia in populations of African origin. Little is known about this risk in older African Caribbean residents in the UK. One difficulty is lack of consensus over an adequate cognitive test battery for this community. Forty-five African Caribbean and 45 age and gender matched white community residents were recruited by household enumeration of an inner London electoral ward. These participants were administered the MMSE during a screening interview. Where possible, this was followed up by tests from the CERAD and CAMCOG neuropsychological batteries, a medical examination, and a structured interview with an informant. Based on these data, a psychiatrist blind to ethnicity independently rated 86 of these participants (41 of the African Caribbeans, all 45 of the whites) as cognitively normal, cognitively impaired, or demented. Of 41 African Caribbeans, 18 (44%) were rated as cognitively normal, 9 (22%) were rated as cognitively impaired, and 14 (34%) were rated as demented. Of the 45 whites, 39 (87%) were rated as cognitively normal, 4 (9%) were rated as cognitively impaired, and 2 (4%) were rated as demented. African Caribbeans scored significantly lower than whites in most cognitive test scores, which was not accounted for by their lower educational and occupational attainment, or their higher frequency of cardiovascular risk factors. African Caribbean elders in the UK appear to be at high risk of cognitive impairment and dementia. However, the influence of potential confounding factors such as socio-economic position and ill-health, and the effect of cultural test bias, cannot be ruled out.

Aged↗
PubMed2000

Decline across different domains of cognitive function in normal ageing: results of a longitudinal population-based study using CAMCOG.

Dementia is an important cause of disability in the elderly. There is evidence that cognitive impairment in dementia is on a continuum with cognitive impairment in the non-demented elderly. In order to investigate this possibility, we need detailed knowledge about the population distribution of cognitive function and change in cognitive function. The aim of this study is to describe the change in different domains of cognitive function over 4 years in a population-based sample of non-demented elderly people, and to investigate the effect of sociodemographic variables and baseline cognitive function on change in each of the cognitive domains. Respondents from two group general practice lists (n = 503) were interviewed using the Cambridge Cognitive Examination (CAMCOG) at the incidence wave of the Cambridge City Over-75 Cohort Study and after a mean time period of 3.9 years. One hundred and thirty five of 212 non-demented subjects seen at follow-up completed the CAMCOG at both interviews. The annual rate of change in total CAMCOG score was -1.6 points per year (p < 0.001). There was statistically significant decline in all of the CAMCOG subscales. Greater decline in the Memory subscale was associated with less education (p = 0.03). Greater decline in the Attention/Calculation subscale was associated with manual social class (p = 0.05). Greater decline in the Perception subscale was associated with older age (p = 0.03). Decline in specific cognitive domains may indicate a reversible phase of cognitive impairment and deserves further investigation.

Aged↗
PubMed2000

Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease.

We have examined the relationships between dementia, loss of synaptic proteins, changes in the cytoskeleton, and deposition of beta-amyloid plaques in the neocortex in a clinicopathologically staged epidemiological cohort using a combination of biochemical and morphometric techniques. We report that loss of synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5 and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic proteins was seen only after the emergence of the full spectrum of tau and beta-amyloid pathology in the neocortex at stage 4, but not in the presence of beta-amyloid plaques alone. Contrary to previous studies, we report increases in the levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated with either unchanged or elevated levels of synaptic proteins in the neocortex. Progressive aggregation of paired helical filament (PHF)-tau protein could be detected biochemically from stage 2 onwards, and this was earliest change relative to the normal aging background defined by Braak stage 1 that we were able to detect in the neocortex. These results are consistent with the possibility that failure of axonal transport associated with early aggregation of tau protein elicits a transient adaptive synaptic response to partial de-afferentation that may be mediated by trophic factors. This early abnormality in cytoskeletal function may contribute directly to the earliest clinically detectable stages of dementia.

Alzheimer Disease↗
PubMed2000

Healthy ageing in urban and rural Britain: a comparison of exercise and diet.

OBJECTIVE: to compare exercise levels, and dietary intake of fruit and vegetables in representative samples of healthy elderly people living in rural and urban areas. DESIGN: two-wave (screening followed by face-to-face interview) cross-sectional survey. SETTING: rural Cambridgeshire and urban Nottingham, UK. PARTICIPANTS: 2041 respondents (1021 in Cambridgeshire; 1020 in Nottingham) sampled from general practitioner lists. MAIN OUTCOME MEASURES: self-rated reports of health, exercise and food frequency. RESULTS: within these samples of healthy elderly people, those living in rural Cambridgeshire were significantly more likely to consume fresh fruit [odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.52-2.16, P < 0.001] and green vegetables (OR = 3.70, 95% CI = 3.07-4.45, P < 0.001) daily in both the summer and winter months. While overall levels of activity were similar for both groups, the structure of activities differed, with the urban sample reporting significantly greater time spent walking. CONCLUSIONS: against current World Health Organisation recommendations for fruit and vegetable consumption, respondents in rural areas reported a substantially 'healthier' diet than their urban peers. On the other hand, urban elderly people may enjoy greater cardiovascular protection from greater time spent walking.

Aged↗
PubMed2000

Very old drivers: findings from a population cohort of people aged 84 and over.

BACKGROUND: Increases in longevity will involve a significant increase among the number of drivers in the very old, who are at greater risk of being involved in road accidents. Data are thus needed from studies of older populations to characterize those still driving, the reasons for giving up and to help formulate appropriate policies for dealing with the problems faced and created by an increase in older drivers. METHODS: A driving questionnaire was administered to surviving members of a cohort comprising a representative sample of individuals aged >/=84, the Cambridge City over 75 Cohort. Out of 546 survivors 404 completed the driving questionnaire at the 9-year follow-up. In addition, subjects were assessed, at baseline and at each follow-up, for cognitive performance using the Mini-Mental State Examination (MMSE) and for physical impairment using the Instrumental of Activities in Daily Living (IADL) scale. RESULTS: Of the sample, 37% had driven in the past, and 8.4% were still driving, the majority regularly. The drivers tended to be younger (mean age 86.6 years), men (71%) and to be married (67.7%). Although physical disability and cognitive impairment are common in this age group, current drivers had few physical limitations on their daily activities and were not impaired on MMSE. None of the current drivers had visual impairment and 22.6% had hearing loss. Of those who had given up driving, 48.5% had given up at the age of >/=80. The commonest reasons for giving up driving were health problems (28.6%), and loss of confidence (17.9%). One-third reported giving up driving on advice. CONCLUSION: A process of self-selection takes place among older drivers. People over the age of 84 who are still driving have generally high levels of physical fitness and mental functioning, although some have some sensory loss. Given the likely increase in the number of older drivers over the next decades, safety will be improved most by strategies aimed at the entire driving population with older drivers in mind, rather than relying on costly screening programmes to identify the relatively small numbers of impaired older people who continue to drive.

Accidents, Traffic↗
PubMed2000

Influence of apolipoprotein E genotype on the risk of cognitive deterioration in moderate drinkers and smokers.

We investigated the risk of cognitive deterioration in relation to alcohol consumption and smoking according to the apolipoprotein E (ApoE) polymorphism. The ApoE epsilon4 allele is an established risk factor for dementia and cognitive impairment. There are also some recent indications that vascular risk factors, including alcohol and tobacco consumption, might play a role in cognition. Our data are from the Epidemiology of Vascular Aging (EVA) study, a prospective study of 1,389 subjects ages 59-71 years at study entry, living the city of Nantes, France, and followed at 4 years after entry. Information on subjects' alcohol and tobacco consumption was collected from a structured questionnaire on food habits. Cognitive performance was assessed by the Mini-Mental State Examination (MMSE). Cognitive deterioration was defined as a decrease of 3 points or more in the Mini-Mental State Examination between study entry and 4-year follow-up. Drinking was associated with a decreased risk of cognitive deterioration in non-ApoE epsilon4 carriers, whereas an opposite association was observed in ApoE epsilon4 carriers. The risk of cognitive deterioration associated with tobacco consumption was also modified according to ApoE genotype, with smokers being at decreased risk of cognitive deterioration among ApoE epsilon4 allele carriers and at increased risk in noncarriers. The effects of alcohol consumption and smoking on the risk of cognitive deterioration appears to be strongly modified by the presence of ApoE epsilon4 allele.

Aged↗
PubMed2000

Neuropathological findings in the very old. Results from the first 101 brains of a population-based longitudinal study of dementing disorders.

We report a unique longitudinal epidemiological study of cognitive decline in the elderly population of the city of Cambridge, UK. A population sample of people aged 75 and over was surveyed between 1984-1996 (n = 2,616) and followed 2.4, 6, and 9 years later. CAMDEX diagnostic criteria were used for clinical assessment, and the neuropathological protocol (in 101 cases) was based on the CERAD method, with additional features to allow Braak staging of neurofibrillary pathology. The main findings are of the heterogeneity of lesions to be found in very old populations, and the existence of considerable overlap in the pathologies found in the demented and nondemented. It seems that white matter (ischemic) pallor an amyloid angiopathy, as well as neuritic plaques, neurofibrillary tangles and Lewy body formation are all lesions that increase the likelihood of dementia.

Age Factors↗
PubMed2000

Psychosocial aetiology of chronic disease: a pragmatic approach to the assessment of lifetime affective morbidity in an EPIC component study.

OBJECTIVES: The Health and Life Experiences Questionnaire (HLEQ) was developed for use in a prospective cohort study of 25,000 men and women living in Norfolk and forms a component study of the European Prospective Investigation into Cancer and Nutrition (EPIC). The HLEQ includes an assessment of mood status over the life course allowing a limited capacity for the imposition of diagnostic criteria to enable eventual evaluation of mental health status for chronic disease outcomes. This paper reports estimates of HLEQ Major Depressive Disorder (MDD) prevalence and compares them with those obtained through interviewer-based methods. In addition evidence for the impact of recall, clustering or cohort effects on these estimates are examined. PARTICIPANTS: 3491 eligible respondents to EPIC in Norfolk, aged 45-74 years, recruited from the first five general practices who completed the HLEQ. MAIN RESULTS: MDD prevalence estimates were found to be closely comparable to those obtained recently (by interview) in the UK and to those lifetime MDD rates determined through international studies. Risk of MDD onset was found to vary with age as expected from earlier studies using interviewer-based assessments. Limited evidence was found to show that the distribution of first onset MDD episodes were compressed during the immediate pre-assessment period. Results were also consistent with previous evidence demonstrating the raised risk of MDD among women and of the decline in gender differences with advancing age. CONCLUSIONS: These results suggest that estimates of putative MDD diagnostic status, derived through the HLEQ, and of associated demographic risk are similar to those derived by more intensive and costly assessment methods. Implications for the future study of MDD both as an outcome and as a risk factor for chronic disease are discussed.

Aged↗
PubMed2000

Socioeconomic status and the expectation of disability in old age: estimates for England.

OBJECTIVES: The longer life expectancy in old age of more privileged socioeconomic groups is well established, but less clear is whether the net effect of additional years of life is a lengthened, stable or reduced duration of disability. Estimates of healthy and disabled life expectancy (using definitions including dependency in activities of daily living and cognitive impairment) were made, contrasting occupational classes I and II (professional and managerial) with the rest. DESIGN: Disability prevalence was estimated from the Medical Research Council Cognitive Function and Ageing study. Sullivan's method was used to calculate health expectancy. SUBJECTS: 10,377 people aged 65 years or over in Cambridgeshire, Newcastle, Nottingham and Oxford. Subjects were classified as disabled if they had evidence of dementia (using the Automated Geriatric Examination Computer Assisted Taxonomy) or scored 11 or more on the modified Townsend Disability scale, at baseline screen. RESULTS: The prevalence of disability overall and need for "constant care" was lower in both men and women in social classes I and II compared with the rest. Men aged 65 to 69 in classes I and II can expect nearly 14 years of life free of disability compared with 11.5 years for those in classes III to V: for women the equivalent expectations are 15.5 and 13.8 years. Men aged 65 to 69 in classes I and II can also expect a shorter duration of disability: 1 year compared with 1.6 years for classes III to V. In women expectation of disability is higher overall, but shows little difference by occupational class. CONCLUSIONS: Relatively privileged socioeconomic groups in England, especially men, can expect fewer years of disability despite longer overall life expectancy. These findings lend weight to optimistic scenarios for the future numbers of older people with disability.

Aged↗
PubMed2000

The ACE gene and Alzheimer's disease susceptibility.

A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimer's disease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significantly different ACE genotype distributions in the case and control groups (p=0.007). Homozygotes for both the I and D alleles were associated with a higher risk compared to DI heterozygotes. While the APOE epsilon4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between the APOE and ACE loci. In addition, no interactions were observed between ACE and gender or age at death of the AD cases. A meta-analysis of all published reports (12 case-control series in total) suggested that both the II and ID ACE genotypes are associated with increased AD risk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.63, OR for DI v DD 1.33, 95% CI=1.14-1.53, p=0.0002).

Aged↗
PubMed1999

Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group.

OBJECTIVE: To study the difference in risk for dementing diseases between men and women. BACKGROUND: Previous studies suggest women have a higher risk for dementia than men. However, these studies include small sample sizes, particularly in the older age groups, when the incidence of dementia is highest. METHODS: Pooled analysis of four population-based prospective cohort studies was performed. The sample included persons 65 years and older, 528 incident cases of dementia, and 28,768 person-years of follow-up. Incident cases were identified in a two-stage procedure in which the total cohort was screened for cognitive impairment, and screen positives underwent detailed diagnostic assessment. Dementia and main subtypes of AD and vascular dementia were diagnosed according to internationally accepted guidelines. Sex- and age-specific incidence rates, and relative and cumulative risks for total dementia, AD, and vascular dementia were calculated using log linear analysis and Poisson regression. RESULTS: There were significant gender differences in the incidence of AD after age 85 years. At 90 years of age, the rate was 81.7 (95% CI, 63.8 to 104.7) in women and 24.0 (95% CI, 10.3 to 55.6) in men. There were no gender differences in rates or risk for vascular dementia. The cumulative risk for 65-year-old women to develop AD at the age of 95 years was 0.22 compared with 0.09 for men. The cumulative risk for developing vascular dementia at the age of 95 years was similar for men and women (0.04). CONCLUSION: Compared with men, women have an increased risk for AD. There are no gender differences in risk for vascular dementia.

Aged↗
PubMed1999

Factors associated with functional decline and improvement in a very elderly community-dwelling population.

The objective of this study was to analyze the factors associated with functional decline and improvement in a community-dwelling population of people aged 75 years and older. A representative sample of elderly people living at home in the city of Sherbrooke (Quebec, Canada) was assessed yearly on three occasions (1991-1993) by a nurse. A health questionnaire, together with standardized instruments measuring disabilities, cognitive status, and depressive mood, was administered on the three assessments. From the 655 subjects who agreed to participate, a total of 504 subjects completed the study. The most important factors associated with functional decline were the number of days off regular activities (odds ratio (OR) = 1.31), the number of hot meals per day (OR = 1.59), and cognitive status (OR = 0.96), whereas weight loss (OR = 0.37) and living alone (OR = 0.54) were significant protective factors. Previous declines in functional autonomy, cognitive state, or mood were not independent risk factors. The most important factors associated with functional improvement were the disability score (OR = 1.08), previous functional decline (OR = 6.06), and decline in the disability score (OR = 1.09). Perceiving health to be worse than it was the previous year was a significant factor against improvement (OR = 0.24). This study identifies risk factors that can be helpful for targeting high-risk subgroups within the very elderly population who may benefit from a preventive program.

Activities of Daily Living↗
PubMed1999

Profile of disability in elderly people: estimates from a longitudinal population study.

OBJECTIVES: To provide estimates of the numbers of cognitively impaired and physically disabled elderly people in England and Wales, subdivided by a range of sociodemographic, dependency, care receipt, and survival variables, to support debates on the form and funding of health and welfare programmes. DESIGN: Interviews at baseline and 2 year follow up plus data on resource use extracted from records for those with disability. SUBJECTS: 10 377 people aged 65 years and over in Cambridgeshire, Newcastle, Nottingham, and Oxford. All estimates weighted to population of England and Wales in 1996. RESULTS: 11% of men and 19% of women aged 65 and over were disabled, totalling 1.3 million people; 38% of these were aged 85 or over and a similar percentage were cognitively impaired. Overall, more than 80% of elderly disabled people needed help on at least a daily basis. Over a third of people with limitations to daily activity living in private households were wholly or partly dependent on formal services for help. 63% of disabled elderly people used acute hospitals during the 2 year follow up, 43% as inpatients. 53% of those with cognitive impairment and limitations to daily activity were living in institutions. CONCLUSIONS: Very elderly people and those with cognitive impairment make up a large proportion of those in need of long term care. A large proportion of even the most disabled elderly people currently live outside institutions and depend on formal services as well as informal care givers. Disabled elderly people use acute hospitals extensively, underlining the interrelations between acute and long term care.

Activities of Daily Living↗
PubMed1999

Rates and risk factors for dementia and Alzheimer's disease: results from EURODEM pooled analyses. EURODEM Incidence Research Group and Work Groups. European Studies of Dementia.

OBJECTIVE: To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma. BACKGROUND: These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled. METHODS: The authors performed a pooled analysis of four European population-based prospective studies of individuals 65 years and older, with 528 incident dementia patients and 28,768 person-years of follow-up. Patients were detected by screening the total cohort with brief cognitive tests, followed by a diagnostic assessment of those who failed the screening tests. Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (revised), and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Incident rates and relative risk (95% CI) express the association of a risk factor for dementia. RESULTS: Incident rates for dementia and AD were similar across studies. The incidence of AD increased with age. At 90 years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000 person-years. Female gender, current smoking (more strongly in men), and low levels of education (more strongly in women) increased the risk of AD significantly. A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly. CONCLUSION: Contrary to previous reports, head trauma was not a risk factor for AD, and smoking did not protect against AD. The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies. Female gender may modify the risk of AD, whether it be via biological or behavioral factors.

Age Distribution↗