Amateur Boxing and Dementia: Cognitive Impairment Within the 35-Year Caerphilly Cohort Study.

OBJECTIVE: To examine the long-term effects of amateur boxing in a representative population sample of men. DESIGN: The sample was examined every 5 years for 35 years. Cognition was assessed repeatedly from the third examination. Previous boxing experience and dementia were assessed at the fifth examination, and dementia assessed subsequently through medical records. SETTING AND ASSESSMENT OF RICK FACTORS: The Caerphilly Prospective Study investigates risk factors for a range of chronic diseases of diseases. These include life style and behavior, together with biological factors relevant to vascular disease. PARTICIPANTS: 1123 adult men aged 45 to 59 years at baseline, followed for 35 years. MAIN OUTCOME MEASURES: Cognitive impairment. RESULTS: A report by a subject of having boxed "seriously" when younger was associated with a 2-fold increase in cognitive impairment [odds ratio (OR) = 2.27; 95% confidence intervals = 1.18-4.38]. For amnestic (Alzheimer-like) impairment, this rises to OR = 2.78 (95% confidence limits 1.37-5.65). Having boxed is associated with an "advancement" in the onset of the dementia (4.8 years; 95% confidence limits 0.9-8.8 years). CONCLUSIONS: Amateur boxing is associated with an increased risk and an earlier onset of cognitive impairment and dementia.

Clinical judgment of GPs for the diagnosis of dementia: a diagnostic test accuracy study.

BACKGROUND: GPs often report using clinical judgment to diagnose dementia. AIM: To investigate the accuracy of GPs' clinical judgment for the diagnosis of dementia. DESIGN & SETTING: Diagnostic test accuracy study, recruiting from 21 practices around Bristol, UK. METHOD: The clinical judgment of the treating GP (index test) was based on the information immediately available at their initial consultation with a person aged ≥70 years who had cognitive symptoms. The reference standard was an assessment by a specialist clinician, based on a standardised clinical examination and made according to the 10th revision of the International Classification of Diseases (ICD-10) criteria for dementia. RESULTS: A total of 240 people were recruited, with a median age of 80 years (interquartile range [IQR] 75-84 years), of whom 126 (53%) were men and 132 (55%) had dementia. The median duration of symptoms was 24 months (IQR 12-36 months) and the median Addenbrooke's Cognitive Examination III (ACE-III) score was 75 (IQR 65-87). GP clinical judgment had sensitivity 56% (95% confidence interval [CI] = 47% to 65%) and specificity 89% (95% CI = 81% to 94%). Positive likelihood ratio was higher in people aged 70-79 years (6.5, 95% CI = 2.9 to 15) compared with people aged ≥80 years (3.6, 95% CI = 1.7 to 7.6), and in women (10.4, 95% CI = 3.4 to 31.7) compared with men (3.2, 95% CI = 1.7 to 6.2), whereas the negative likelihood ratio was similar in all groups. CONCLUSION: A GP clinical judgment of dementia is specific, but confirmatory testing is needed to exclude dementia in symptomatic people whom GPs judge as not having dementia.

Troponin and BNP are markers for subsequent non-ischaemic congestive heart failure: the Caerphilly Prospective Study (CaPS).

Objective: To examine the long-term predictive value of 28 biomarkers for subsequent non-ischaemic congestive heart failure (CHF) and separately for other cardiovascular outcomes (myocardial infarction (MI) and stroke). Methods: The Caerphilly Prospective Study recruited 2171 men aged 55-69 years from the general population in 1989-1993; men were screened for evidence of cardiovascular disease (CVD) and followed for clinical cardiovascular events. Fasting blood samples were stored at -70°C until assayed for novel biomarkers in 2010-2013. A competing risks proportional hazards regression analysis was used to estimate subhazard ratios (SHRs) for each biomarker for each cardiovascular outcome. Results: During follow-up (average 13 years), only new, initial events were evaluated in the whole cohort: 584 MIs, 313 strokes and 261 episodes of CHF (not associated with acute MI). In a subcohort of men who had no clinical history or evidence of CVD at baseline examination (n=1279) those in the top third of the distributions of troponin and B-type natriuretic peptide (BNP) showed a threefold increase in risk for subsequent CHF as a first event after adjustment for all conventional risk factors (SHRs 3.37, 95% CI 1.39 to 8.14 and 3.23, 95% CI 1.45 to 7.23), respectively, in contrast to moderate elevations in risk for acute MI (troponin SHR 1.63, 95% CI 1.10 to 2.41) and for stroke (BNP SHR 1.75 95% CI 1.06 to 2.88). Conclusion: Troponin and BNP could be considered as potentially useful screening tools to detect subjects without prior CVD at increased risk of developing CHF in subsequent years in addition to having lesser roles for predicting subsequent MI (troponin) or stroke (BNP).

Healthy living and cancer: evidence from UK Biobank.

CONTEXT: UK Biobank is a prospective study of half a million subjects, almost all aged 40-69 years, identified in 22 centres across the UK during 2006-2010. OBJECTIVE: A healthy lifestyle has been described as 'better than any pill, and no side effects [5]. We therefore examined the relationships between healthy behaviours: low alcohol intake, non-smoking, healthy BMI, physical activity and a healthy diet, and the risk of all cancers, colon, breast and prostate cancers in a large dataset. METHOD: Data on lifestyle behaviours were provided by 343,150 subjects, and height and weight were measured at recruitment. 14,285 subjects were diagnosed with cancer during a median of 5.1 years of follow-up. RESULTS: Compared with subjects who followed none or a single healthy behaviour, a healthy lifestyle based on all five behaviours was associated with a reduction of about one-third in incident cancer (hazard ratio [HR] 0.68; 95% confidence intervals [CI] 0.63-0.74). Colorectal cancer was reduced in subjects following the five behaviours by about one-quarter (HR 0.75; 95% CI 0.58-0.97), and breast cancer by about one-third (HR 0.65; 95% CI 0.52-0.83). The association between a healthy lifestyle and prostate cancer suggested a significant increase in risk, but this can be attributed to bias consequent on inequalities in the uptake of the prostate specific antigen screening test. CONCLUSIONS: Taken together with reported reductions in diabetes, vascular disease and dementia, it is clearly important that every effort is taken to promote healthy lifestyles throughout the population, and it is pointed out that cancer and other screening clinics afford 'teachable moments' for the promotion of a healthy lifestyle.

Does anxiety affect risk of dementia? Findings from the Caerphilly Prospective Study.

OBJECTIVE: To examine the association of anxiety with incident dementia and cognitive impairment not dementia (CIND). METHODS: We conducted a prospective study of men aged 48 to 67 years at baseline anxiety assessment; we measured cognition 17 years later. We studied 1481 men who were either eligible for examination or were known to have dementia. Trait Anxiety was assessed using the Spielberger State Trait Anxiety Inventory. Psychological distress was assessed using the 30-item general health questionnaire. Cognitive screening was followed by a clinical examination. Medical notes and death certificates of those not seen were also examined. Outcomes were CIND and Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) dementia. RESULTS: Of 1160 men who were cognitively screened, 174 cases of CIND and 69 cases of dementia were identified. A further 21 cases of dementia were identified from medical records. After adjustment for age, vascular risk factors and premorbid cognitive function associations with higher anxiety (31st-95th centile) were for CIND odds ratio (OR) 2.31 (95% Confidence Interval (CI) = 1.20-4.44) and for dementia OR 2.37 (95% CI = 0.98-5.71). These associations were slightly stronger for nonvascular (OR = 2.45; 95% CI = 1.28-4.68) than for vascular impairment (OR = 1.94; 95% CI = 0.77-4.89). Analyses of change in cognitive performance, assessed by the Cambridge Cognitive Examination of the Elderly subscales found some evidence for decline in learning memory with higher anxiety score (b(age adj) = -0.291 (-0.551, -0.032), but not for any other subscale. CONCLUSIONS: Anxiety is a risk factor for CIND and dementia. The extent to which the association is independent of depression and whether or not it is causal requires further study.

Long-term effects of Abeta42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial.

BACKGROUND: Immunisation of patients with Alzheimer's disease with full-length amyloid-beta peptide (Abeta(42)) can clear amyloid plaques from the brain. Our aim was to assess the relation between Abeta(42) immune response, degree of plaque removal, and long-term clinical outcomes. METHODS: In June, 2003, consent for long-term clinical follow-up, post-mortem neuropathological examination, or both, was sought from 80 patients (or their carers) who had entered a phase I randomised, placebo-controlled trial of immunisation with Abeta(42) (AN1792, Elan Pharmaceuticals) in September, 2000. The follow-up study was completed in September, 2006. Plaques were assessed in terms of the percentage area of the cortex with Abeta immunostaining (Abeta load) and in terms of characteristic histological features reflecting plaque removal. Survival of all 80 individuals until severe dementia or death was assessed with a Cox proportional hazard model. FINDINGS: 20 participants--15 in the AN1792 group, five in the placebo group--died before follow-up started. A further 22 patients--19 in the AN1792 group, three in the placebo group--died during follow-up. Nine of the deceased patients, all in the AN1792 group, had given consent for post-mortem analysis; one of these who did not die with Alzheimer's disease was excluded. In the remaining eight participants who received immunisation and who were examined neuropathologically, mean Abeta load was lower than in an unimmunised control group that was matched for age at death (2.1% [SE 0.7] in treated participants vs 5.1% [0.9] in controls; mean difference 3.0%, 95% CI 0.6-5.4; p=0.02). Although there was considerable variation in Abeta load and degree of plaque removal among immunised participants, the degree of plaque removal varied significantly with mean antibody response attained during the treatment study period (Kruskal-Wallis p=0.02). Seven of the eight immunised patients who underwent post-mortem assessment, including those with virtually complete plaque removal, had severe end stage dementia before death. In the whole cohort, there was no evidence of improved survival (hazard ratio 0.93, 95% CI 0.43-3.11; p=0.86) or of an improvement in the time to severe dementia (1.18, 0.45-3.11; p=0.73) in the AN1792 group versus the placebo group. INTERPRETATION: Although immunisation with Abeta(42) resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not prevent progressive neurodegeneration.

Glucoregulation has greater impact on cognitive performance than macro-vascular disease in men with type 2 diabetes: data from the Caerphilly study.

OBJECTIVE: To compare vascular and glucose related mechanisms of type 2 diabetes on cognitive performance. RESEARCH DESIGN AND METHODS: A cross-sectional observational study of type 2 diabetes defined by non insulin dependant self-report diabetes or fasting blood glucose < or = 7.0 mmol/l of 2205 men eligible for the third phase of the Caerphilly Collaborative Heart Disease Study. Men were aged 55-69 years at time of testing. Tests of cognitive function included NART (crystallised IQ), AH4 (fluid IQ), verbal fluency (executive function) Cambridge Cognitive Examination (CAMCOG) and Mini Mental State Examination (MMSE) (global function), four choice serial reaction time (psychomotor function) and memory. Men with prior stroke were omitted from the analysis. RESULTS: Men with diabetes showed cognitive deficits for verbal fluency, National Adult Reacting Test (NART) and AH4. Adjusting for vascular risk factors had minimal effect. Including blood glucose removed the deficit for verbal fluency and NART but the effect on AH4 score (-2.58; 95% CI: -5.0, -0.1, p = 0.039) was retained. More detailed analyses of AH4 score on men with diabetes showed a curvilinear relationship indicating that men with both low and high glucose levels had worse performance (AH4 = -66 + 80 log(e) glucose - 18 log(e )glucose(2); 95% CI: -29, -6; p=0.002). CONCLUSIONS: These data identify a direct effect of glucose regulation on cognitive performance associated with diabetes in a population sample. These data suggest that an effect of glucose regulation on cognitive performance in diabetes is distinct from any effect of macro-vascular disease.

Cognitive, global, and functional benefits of donepezil in Alzheimer's disease and vascular dementia: results from large-scale clinical trials.

Alzheimer's disease (AD) and vascular dementia (VaD) are both associated with deficits in cholinergic neurotransmission that are amenable to therapeutic intervention. The cholinesterase inhibitor, donepezil, is clinically effective in both AD and VaD. Results from a 10-study metaanalysis of donepezil (5 or 10 mg/day) in AD and a two-study combined analysis of donepezil (5 or 10 mg/day) in VaD are presented to compare patient characteristics and donepezil treatment outcomes. The analyzed studies were randomized, placebo-controlled, and of up to 24 weeks duration. In both AD and VaD, donepezil provided significant benefits compared with placebo on measures of cognition and global function. Placebo-treated AD patients showed a decline in cognition and global function, whereas placebo-treated VaD patients remained stable, suggesting treatment effects of donepezil in VaD were driven by improvement rather than stabilization or reduced decline. More VaD patients than AD patients received concomitant medications. Cardiovascular adverse events were more common in VaD than AD patients but were not increased by donepezil. In conclusion, although there are differences between AD and VaD patients in comorbid conditions and concomitant medications, donepezil is effective and well tolerated in both types of dementia.

The effects of saliency and task difficulty on visual search performance in ageing and Alzheimer's disease.

We asked whether the poor performance on visual search tasks typical of patients with Alzheimer's disease (AD) is the result of a selective deficit in the ability to shift attention from item to item, or the consequence of an inefficient processing of each item within the search set. We attempted to manipulate the ease of attention shifting and item processing in a visual search task by manipulating target salience and task difficulty, respectively. Significant effects of both target saliency and task difficulty for both AD patients and age-matched controls were obtained, with the AD group displaying greater effects of both of these manipulations than the controls. This interaction remained even when the reaction time data were log-transformed to account for the overall slower reaction times of the AD group. We conclude that inefficiency in visual search tasks in AD probably represents the product of both attention shifting and target processing factors.

Spatial shifts in visual attention in normal ageing and dementia of the Alzheimer type.

Using a spatial-cueing paradigm, we assessed the ability of Alzheimer's disease patients, age-matched controls and younger participants to use cues to guide attention to the location indicated by the cue. In separate experiments, we attempted to isolate cues that attract attention automatically (exogenous cueing) and those that require the wilful movement of attention (endogenous cues). We found significant cueing effects for all three groups of participants for both types of cue. However, the group with Alzheimer's disease showed far greater cueing effects when using an exogenous cue, whilst no difference between group's ability to use the cue was found for the endogenous cue. No differences in cueing were found for either cue type as a function of normal ageing. We further tested whether the differences in cueing found in the group with Alzheimer's disease was due to a generalised slowing of function. After transforming the data to take account of the overall slowing of all responses in this group, we still found significant differences between this group and the control groups. We conclude that patients with Alzheimer's disease have an abnormality in automatic, but not controlled visuospatial attention.

Vascular disease and cognitive function in older men in the Caerphilly cohort.

OBJECTIVES: Stroke can impair cognitive function, but the associations between other manifestations of vascular disease and cognitive function have not been adequately studied in representative population samples of subjects. We report the associations between cardiac and peripheral vascular disease and cognitive function for a large representative sample of men in Caerphilly, South Wales, UK. DESIGN: The Caerphilly cohort is the basis of on-going studies of vascular disease, of cognitive function and of predictors of these. We have made intensive attempts to identify all cases of vascular disease: myocardial infarction, angina, ECG ischaemia, peripheral vascular disease (intermittent claudication) and stroke. Here we present data on associations between vascular disease and cognitive function. SETTING: The study is based upon a representative population sample of over 1,500 men in South Wales, aged 55-69 years when cognitive function was measured. The men, and hospital and GP notes relating to them, had been repeatedly examined for evidence of vascular disease during the previous ten years. MAIN OUTCOME MEASURES: Standard tests of cognitive function: the AH4, CAMCOG, MMSE and choice reaction time. RESULTS: After the omission of men who had had a stroke, we detected significant associations between cognitive function and the presence of angina, ECG ischaemia, past myocardial infarction and intermittent claudication. The strength of the associations between cognitive function and the various manifestations of vascular disease were similar, and the various cognitive function tests showed effects of similar size. Overall, cardiac and peripheral vascular disease is associated with a significant reduction in cognitive function equivalent to about one sixth of the standard deviation of a number of tests of cognitive function. The size of this effect is roughly equivalent to the decline in cognitive performance over five years of ageing. CONCLUSIONS: Subjects with evidence of cardiac or peripheral vascular disease have on average a significant reduction in cognitive function equivalent to about four or five years of additional age. The effect of long-term, low-dose aspirin on cognitive decline should now be tested.