Search PubMed⌕ Search

Biomedical subjects

C Brayne

Publications and source records attributed to C Brayne.

At least 19 recordsLinked to original sources
PubMed2006

A systematic review of depression and mental illness preceding Parkinson's disease.

Depression has been reported in several studies to be more common in Parkinson's disease (PD) patients than in the general population, and there may be overlap in the pathophysiology of the two conditions. Anxiety and other mental disorders have also been examined for possible association with PD because of their effects on the brain. MEDLINE, EMBASE and PSYCHINFO databases were searched systematically for existing systematic reviews or meta-analyses and primary research articles. Past studies and reviews have focused on co-morbidity of depression or mental disorders and PD, but as yet there have been no systematic reviews of the evidence that these conditions precede PD. Articles without robust methodology were excluded by specified criteria, based on published quality scoring criteria. Three cohort studies, one nested case-control study, and 10 case-control studies are included in the current systematic review. Premorbid depression was significantly more common in PD patients than in those without a diagnosis of PD in five of six case-control studies and three cohort studies. Premorbid anxiety may also be associated with PD although the evidence was not as strong. A few studies have looked at dementia as a co-morbid or sequel, but never as a predictor of PD.

Depression↗
PubMed2005

Depression in the elderly: pathological study of raphe and locus ceruleus.

Depressive symptoms in the elderly are common and disabling and constitute a risk factor for the development of Alzheimer's disease (AD). One hypothesis worth exploring is that depression in the elderly is related to development of AD pathology at subcortical sites before such pathology develops in the hippocampus and neocortex. We describe here an autopsy study of the locus ceruleus (LC) and raphe nuclei (RN) in nine subjects with depression and 18 age and sex matched controls that were included in a community-based study of cognitive function and ageing (MRC-CFAS). We found no relationship between depression and (1) mean counts of serotonergic or total RN neuronal profiles (2) noradrenergic or total LC neuronal profiles (3) counts of neurofibrillary tangles in these nuclei, or (4) size of neurones in the RN. Nor were these parameters related to age or sex of the subjects. We conclude that depression in the elderly is unlikely to be related to RN or LC neurone counts or RN cell size or to AD-type pathology in these nuclei. However, because of the small numbers of cases studied and our inability to carry out a full stereological study because of tissue limitations the findings are preliminary.

Age Factors↗
PubMed2004

Effect of smoking on global cognitive function in nondemented elderly.

BACKGROUND: Contrary to early case-control studies that suggested smoking protects against Alzheimer disease (AD), recent prospective studies have shown that elderly who smoke may be at increased risk for dementia. OBJECTIVE: To examine prospectively the effect of smoking on cognition in nondemented elderly. METHOD: In a multicenter cohort, the European Community Concerted Action Epidemiology of Dementia (EURODEM), including the Odense, Personnes Agées Quid (Paquid), Rotterdam, and Medical Research Council: Ageing in Liverpool Project-Health Aspects (MRC ALPHA) Studies, 17,610 persons aged 65 and over were screened and examined for dementia. After an average 2.3 years of follow-up, 11,003 nondemented participants were retested. Excluding incident dementia cases and those without baseline information on smoking gave an analytical sample of 9,209 persons. Average yearly decline in Mini-Mental State Examination (MMSE) score was compared among groups, adjusting for age, sex, baseline MMSE, education, type of residence, and history of myocardial infarction or stroke. RESULTS: MMSE score of persons who never smoked on average declined 0.03 point/year. The adjusted decline of former smokers was 0.03 point greater and of current smokers 0.13 point greater than never smokers (p < 0.001). Higher rates of decline by smoking were found in men and women, persons with and without family history of dementia, and in three of four participating studies. Higher cigarette pack-year exposure was correlated with a significantly higher rate of decline. CONCLUSION: Smoking may accelerate cognitive decline in nondemented elderly.

Age Distribution↗
PubMed2002

The prevalence of frontotemporal dementia.

OBJECTIVE: To estimate the prevalence of frontotemporal dementia (FTD) and other degenerative early-onset dementias in a geographically defined population. BACKGROUND: Early-onset dementia (at age <65 years) results in high psychiatric morbidity and caregiver burden. Prevalence figures are available for early-onset AD but not for FTD, a dementia that is almost invariably of early onset. METHODS: Case ascertainment was by review of case records of three specialist clinic databases and inpatient admissions at a university hospital in Cambridge, United Kingdom, for patients with dementia who were <65 years of age, living in Cambridge City or East or South Cambridgeshire (population 326,019) on May 30, 2000. All the relevant health services in the area were also contacted for potential cases. Diagnosis of various dementias was based on published criteria. All patients with potential FTD were examined by the study investigators and underwent structural neuroimaging. The 1998 population estimates for the area were used to calculate age and sex prevalence with confidence intervals for AD, FTD, and other causes of dementia. RESULTS: A total of 108 patients (66 men and 42 women) with dementia with onset before they were 65 years of age were identified, of whom 60 were <65 years on the census date, giving an overall prevalence of 81 (95% CI, 62.8 to 104.5) per 100,000 in the 45- to 64-year age group. The prevalences of early-onset FTD and AD were the same: 15 per 100,000 (8.4 to 27.0) in the 45- to 64-year-old population. The mean age at onset of FTD was 52.8 years and there was a striking male preponderance (14:3). It is possible case ascertainment methods resulted in a relative underrepresentation of some forms of dementia. CONCLUSIONS: Frontotemporal dementia is a more common cause of early-onset dementia than previously recognized and appears to be more common in men.

Age of Onset↗
PubMed2002

Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population.

BACKGROUND: Apolipoprotein E (APOE) polymorphisms are unequivocally associated with risk for Alzheimer's disease (AD). It is crucial to understand how this genetic factor affects dementia risk in the general population, as well as in narrowly diagnosed, selected, patient groups. METHODS: We assessed the cross sectional association between APOE genotype and dementia status in a community based sample, the MRC Cognitive Function and Ageing Study (MRC CFAS). In addition, we tested the effects of APOE genotypes on the differences in MMSE scores between the first and third assessment waves (about six years apart), an index of cognitive decline. RESULTS: The APOE epsilon4 allele conferred increased risk for dementia (OR=1.5, 95% CI=1.1 to 2.2) compared to epsilon3 in the MRC CFAS sample. Compared with APOE epsilon3/epsilon 3 subjects, those with the epsilon3/epsilon4 genotypes were not at significantly higher risk for dementia (OR=1.1, 95% CI=0.6 to 1.9), although epsilon4/epsilon4 subjects were (OR= 3.8, 95% CI=1.0 to 14.0). Risk estimates were not different between men and women. Notably, our risk estimates for dementia were significantly lower than those reported for a diagnosis of Alzheimer's disease. MMSE scores at wave 3 and the difference in MMSE between baseline and at the third assessment wave were not different across APOE genotypes. INTERPRETATION: The APOE epsilon4 allele is a weaker predictor for dementia in the general population than for AD. This may be because dementia can be caused by non-AD pathological processes and because most prevalent dementia occurs at an age when the APOE epsilon4 effect on AD risk (and therefore dementia) has started to decline.

Aged↗
PubMed2002

The genetic basis of Parkinson's disease.

Although the mechanisms underlying neurodegeneration in Parkinson's disease are not fully understood, considerable evidence suggests that genetic factors can influence susceptibility to the disease. In this article, we critically review this evidence and examine studies estimating patterns of inheritance. In a few families, Parkinson's disease is clearly inherited in a Mendelian fashion, and in some of these the disease causing genes have already been identified. Possible pathogenic mechanisms by which these genes cause Parkinson's disease are discussed. Further candidate genes and systematic efforts to identify genes influencing susceptibility to the disease in general are also summarised. The identification of such susceptibility genes will eventually enable us to more accurately classify this complex disease.

Chromosome Aberrations↗
PubMed2001

Alzheimer disease is not associated with polymorphisms in the angiotensinogen and renin genes.

Hypertension has been implicated as a risk factor for Alzheimer disease (AD) and dementia in epidemiological studies of humans. It is thus possible that there are common genetic determinants for hypertension and AD. Epidemiological, clinical, and experimental data suggest that the renin-angiotensin-aldosterone system is a critical regulator of blood pressure. The presence of an MboI site in an RFLP in the renin gene and the Thr at the Met/Thr polymorphism at codon 235 (M235T) of the angiotensinogen gene have been reported to be associated with hypertension. These variants were studied in autopsy-confirmed AD cases and matched controls from the U.K. While no association was detected with the renin polymorphism, a weak deleterious effect was observed in cases homozygous for the angiotensinogen Thr allele. However, this association was not observed in a French cohort of clinically diagnosed AD cases and controls, suggesting that the initial observation was a type I error. Thus, these polymorphisms are unlikely to be associated with AD risk.

Aged↗
PubMed2001

The BACE gene: genomic structure and candidate gene study in late-onset Alzheimer's disease.

Alzheimer's disease (AD) pathology is characterized by beta-amyloid plaques and neurofibrillary tangles. Studies of autosomal dominant early-onset AD mutations suggest that beta-amyloid overproduction is sufficient to cause AD. Recently, the BACE gene, which encodes beta-secretase, the rate limiting enzyme in beta-amyloid formation, has been identified. Since this gene is a strong candidate gene for late-onset AD because of its function, we have characterized its genomic organization and identified two polymorphisms. Neither of these polymorphisms were associated with AD risk in genetic association studies comparing autopsy-confirmed late-onset AD cases and age-matched non-demented controls. Thus, we find no evidence that this locus influences risk for late-onset AD.

3' Untranslated Regions↗
PubMed2001

Cognitive function in UK community-dwelling African Caribbean elders: normative data for a test battery.

Many 'first generation' African Caribbean residents in the UK have now reached ages where risk of cognitive impairment and dementia starts to increase. In addition, conditions which may impair cognitive function, such as hypertension, diabetes and stroke, have high prevalence rates in African Caribbean populations. However, there is a lack of normative data for cognitive tests in this ethnic group. Cognitive assessment was carried out in a south London community population of 285 African Caribbean participants aged 55-75 years. Tests were drawn principally from the consortium to establish a registry for Alzheimer's disease (CERAD) battery (Boston Naming Test, verbal fluency, word list recall, and Trailmaking Tests A and B) and also included orientation items from the Mini-Mental State Examination (MMSE) and the Clock Drawing Test. Independent effects of age, sex, education and occupation were identified on scores for most but not all cognitive tests. Compared with normative data for African American populations, lower scores on verbal fluency and the Boston Naming Test were observed but scores on memory tests were comparable. Normative data for the tests are presented, stratified by level of education.

Aged↗
PubMed2001

Vascular risk and cognitive impairment in an older, British, African-Caribbean population.

OBJECTIVES: In an older, British, African-Caribbean population with high prevalence rates of hypertension and diabetes mellitus, we ascertained clinical vascular disease (stroke or ischemic heart disease) and vascular risk (including hypertension, diabetes, and lipid profile) and investigated their associations with cognitive impairment. DESIGN: Cross-sectional community-based study. SETTING: The sample was drawn from registration lists for seven primary care services in south London, United Kingdom. PARTICIPANTS: 278 individuals, age 55 to 75, who were born in a Caribbean nation. MEASUREMENTS: Participants were interviewed and examined for cardiovascular risk factors, including a blood test for lipid profile and fibrinogen. A battery of 11 psychometric tests was administered blind to medical status. Cognitive impairment was defined on the basis of a composite measure derived from individual test scores. RESULTS: Seventy-nine (28%) subjects were classified as having relative cognitive impairment and were compared with the remainder of the sample. Marked differences were seen between low and normal/high educational levels in the strength of associations between measures of vascular risk and cognitive impairment. Hypertension, diabetes, and raised triglycerides were significant factors in those with lower levels of education. Low fibrinogen (negatively associated), high cholesterol, and manual occupation were significant factors in those with normal/high levels of education. Physical exercise was negatively associated with cognitive impairment: an association that persisted after adjustment for age, occupation, depression, and physical disability and after excluding subjects with the most severe imipairment. CONCLUSION: Measures of vascular risk were associated with relative cognitive impairment in this population. These associations were modified by previous educational attainment. Physical activity was negatively associated with cognitive impairment.

Black or African American↗
PubMed2001

Health and ill-health in the older population in England and Wales. The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS).

OBJECTIVE: to provide a profile of disorders and disabilities in the older population. DESIGN: the MRC CFAS drew population samples of people aged 64 years and over from Family Health Service Authority lists at five sites and asked participants about sociodemographic variables, physical and cognitive health and activities of daily living, We calculated the prevalence of co-morbidity from the number of different types of complaint or disability (physical, functional and cognitive), and calculated healthy life expectancies in each of these co-morbid states. SETTING: three urban (Newcastle, Nottingham and Oxford) and two rural sites (Cambridgeshire and Gwynedd). RESULTS: the prevalence of morbidity is low at the youngest ages, as is co-morbidity. Women have consistently greater morbidity than men. Morbidity increases sharply with age, with a more dramatic rise in women. Life expectancy without any morbidity is short at all ages over 64, with the number of years expected with two or more areas affected virtually constant up to 90 years. As a proportion of remaining life expectancy, the period of time spent with two or more areas affected rises by the age of 90 to 30% in men and 60% in women. CONCLUSIONS: preventive programmes for the older population should take into account the large differences between the young old, the middle old and the old old. Our study provides a baseline against which to compare future changes in health in older populations, as well as benchmark expectancies for the UK population.

Activities of Daily Living↗
PubMed2001

Cognition and survival: an exploration in a large multicentre study of the population aged 65 years and over.

BACKGROUND: Understanding the patterns in determinants of survival becomes increasingly important as the population ages. Dementia is known to shorten survival as is impaired cognition. Whether this is a continuous phenomenon and independent of other explanatory variables is less clear. OBJECTIVES: To examine a population-based dataset in which a measure of cognitive function (Mini-Mental State Examination [MMSE]), self-reported physical health and lifestyle variables were measured at outset, with monitoring for mortality thereafter. METHODS: The five identical sites of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) were analysed, with populations in rural Cambridgeshire, Gwynedd, Newcastle, Nottingham and Oxford. Survival curves were modelled and stratified analyses carried out, with physical disease, sociodemographic variables and lifestyle variables as covariates. RESULTS: There was a strong and consistent reduction in survival probability for each decrement in MMSE. Adjustment for known confounders did not alter this pattern. Social class and education in particular had no additional effect. Self-reported health was the only other associated variable. CONCLUSION: Cognitive function appears to be a marker of capacity for survival in the UK. Terminal decline can account for some of this. Actuarial survival provided here can give carers and service providers an idea of prognosis at given ages and levels of cognition, and provide baseline data for those planning interventions in similar groups.

Aged↗
PubMed2001

Genetic association of an LBP-1c/CP2/LSF gene polymorphism with late onset Alzheimer's disease.

OBJECTIVES: The only locus unequivocally associated with late onset Alzheimer's disease (AD) risk is APOE. However, this locus accounts for less than half the genetic variance. A recent study suggested that the A allele of the 3'UTR biallelic polymorphism in the LBP-1c/CP2/LSF gene was associated with reduced AD risk. Samples were diagnosed predominantly by clinical rather than pathological criteria. We have sought to replicate this finding in a series of necropsy confirmed, late onset AD cases and non-demented controls. METHODS: The 3'UTR polymorphism in the LBP-1c/CP2/LSF gene was typed in 216 necropsy confirmed AD cases and 301 non-demented controls aged >73 years. RESULTS: We found different LBP-1c/CP2/LSF allele distributions in our AD cases and controls (p=0.048); the A allele was associated with reduced AD risk. The allele and genotype frequencies observed in our cases and controls were similar to those previously reported. No significant effects emerged when the data were adjusted for age, sex, or apoE epsilon4 carrier status. CONCLUSIONS: Our data support LBP-1c/CP2/LSF as a candidate gene/risk factor for AD and provide justification for future studies to investigate the role of this gene in Alzheimer's disease.

Age of Onset↗
PubMed2001

Exploring the impact of prevalence and mortality on incidence of dementia in the oldest old: the sensitivity of a deterministic approach.

BACKGROUND: There has been considerable debate about whether dementia is an age-related or an aging-related phenomenon. When the evidence is restricted to prevalence data, the inferences are not sound because incidence, mortality and differential mortality are not taken into account. The aim of the paper is to demonstrate the use and sensitivity of a deterministic model based on the relationship between mortality, incidence and prevalence with the example of the chronic disease dementia. DESIGN: The simple deterministic model used here allows the calculation of one component given the other three. The sensitivity of calculated incidence to individual and combined changes in mortality, differential mortality (as measured by the mortality odds ratio) and prevalence is examined using published data. MAIN RESULTS: Calculated incidence continues to increase with age despite extreme but plausible changes in each of the other components. Calculated incidence declines amongst the oldest old only when the changes are combined. CONCLUSION: The deterministic model is shown to provide robust interrogation of the relationship between prevalence, incidence and survival. The effect incidence and survival have on the age-related and aging-related debate is illustrated. Only with extreme assumptions can the incidence of dementia be lessened. Clearly, more information on the oldest old is needed, but incidence studies of sufficient size at such great ages are problematic, and therefore there is a need to use flexible models for maximising the value of empirical data.

Aged↗
PubMed2001

Stroke, vascular risk factors and depression: Cross-sectional study in a UK Caribbean-born population.

BACKGROUND: Stroke, hypertension and diabetes are common in older Caribbean-born populations in the UK who may be at risk of depression secondary to vascular disease. AIMS: We examined the association between stroke, vascular risk factors and depression in a community-based Caribbean-born population aged 55-75 years. METHOD: Vascular risk factors were identified by interview, examination and blood tests. Depression was categorised using the Geriatric Depression Scale. Disablement was assessed as a potential mediating factor. RESULTS: Physical illness and disablement were strongly associated with depression, independent of disablement. Previous stroke was associated with depression, independent of disablement. No vascular risk factors were associated with depression. CONCLUSIONS: The risk of depression associated with stroke was not explained by disablement. However, the hypothesis that vascular risk factors are important in the genesis of depression was not supported.

Age Distribution↗
PubMed2001

Depression, APOE genotype and subjective memory impairment: a cross-sectional study in an African-Caribbean population.

BACKGROUND: Subjective memory impairment (SMI) is common in older populations but its aetiology and clinical significance is uncertain. Depression has been reported to be strongly associated with SMI. Associations with objective cognitive impairment are less clear cut. Other factors suggested to be associated with SMI include poor physical health and the apolipoprotein E (APOE) epsilon4 allele. Studies of SMI have been predominantly confined to white Caucasian populations. METHOD: A community study was carried out in a UK African-Caribbean population aged 55-75, sampled from primary care lists. Twenty-three per cent were classified with SMI. Depression was defined using the 10-item Geriatric Depression Scale. Other aetiological factors investigated were education, objective cognitive function, APOE genotype, disablement and vascular disease/risk. The principal analysis was restricted to 243 participants scoring > 20 on the Mini-Mental State Examination (85%). A second analysis included all 290 participants. RESULTS: Depression, self-reported physical impairment and APOE epsilon4 were associated with SMI. The association between SMI and physical impairment was not explained by depression, vascular disease/risk, or disability/handicap. The association between epsilon4 and SMI increased as MMSE scores decreased and was particularly strong in those with depression. The epsilon4 allele was present in 69% (95% CI 41-89%) of those with depression and SMI compared with 28% (20-36%) of those with neither. CONCLUSIONS: Depression may not be a sufficient explanation for subjective memory complaints. Memory complaints in the presence of depression are associated with high prevalence of epsilon4 and therefore, presumably, a raised risk of subsequent dementia.

Aged↗