Explore the vast range of titles available.

Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death.Design Systematic review and meta-analysis.Data sources PubMed from 1966 to 23 November 2009.Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death.Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome.Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested.Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.

Objectives To relate cancer since entry into the Framingham Heart Study with the risk of incident Alzheimer’s disease and to estimate the risk of incident cancer among participants with and without Alzheimer’s disease.Design Community based prospective cohort study; nested age and sex matched case-control study. Setting Framingham Heart Study, USA.Participants 1278 participants with and without a history of cancer who were aged 65 or more and free of dementia at baseline (1986-90). Main outcome measures Hazard ratios and 95% confidence intervals for the risks of Alzheimer’s disease and cancer.Results Over a mean follow-up of 10 years, 221 cases of probable Alzheimer’s disease were diagnosed. Cancer survivors had a lower risk of probable Alzheimer’s disease (hazard ratio 0.67, 95% confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast with their decreased risk of Alzheimer’s disease, survivors of smoking related cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the nested case-control analysis, participants with probable Alzheimer’s disease had a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference participants, as did participants with any Alzheimer’s disease (0.38) and any dementia (0.44).Conclusions Cancer survivors had a lower risk of Alzheimer’s disease than those without cancer, and patients with Alzheimer’s disease had a lower risk of incident cancer. The risk of Alzheimer’s disease was lowest in survivors of smoking related cancers, and was not primarily explained by survival bias. This pattern for cancer is similar to that seen in Parkinson’s disease and suggests an inverse association between cancer and neurodegeneration.

Objectives To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers.Design Observational multicentre study.Setting Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals).Participants 3056 intensive care patients aged 18 years or over.Main outcome measure Development of delirium (defined as at least one positive delirium screening) during patients’ stay in intensive care.Results The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors—age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses’ and physicians’ predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both.Conclusion The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures.Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study).

Objective To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes.Design Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality.Setting Nursing homes in the United States.Participants 75 445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥65, were eligible for Medicaid, and lived in a nursing home in 2001-5.Main outcome measures Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders.Results Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine.Conclusions Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Objectives The Newcastle 85+ Study aims to systematically study the clinical, biological, and psychosocial attributes of an unselected cohort of 85 year olds and to examine subsequent health trajectories as the cohort ages; health at baseline is reported.Design Cross sectional analysis of baseline data from a cohort study.Setting Newcastle upon Tyne and North Tyneside primary care trusts, United Kingdom.Participants 1042 people born in 1921 and registered with the participating general practices.Main outcome measures Detailed health assessment and review of general practice records (disease, medication, and use of general practice services); participants could decline elements of the protocol. Results Of the 1453 eligible people, 851 (58.6%) were recruited to health assessment plus record review, 188 (12.9%) to record review only, and 3 (0.2%) to health assessment only. Data from record review are reported on a maximum of 1030 and from health assessment on a maximum of 853; individual denominators differ owing to withdrawal and missing values. Of the health assessment sample (n=853), 62.1% (n=530) were women and 10.4% (n=89) were in institutional care. The most prevalent diseases were hypertension (57.5%, 592/1030) and osteoarthritis (51.8%, 534/1030). Moderate or severe cognitive impairment was present in 11.7% (96/824) of participants, severe or profound urinary incontinence in 21.3% (173/813), hearing impairment in 59.6% (505/848), and visual impairment in 37.2% (309/831). Health assessment identified participants with possible disease but without a previous diagnosis in their medical record for hypertension (25.1%, 206/821), ischaemic heart disease (12.6%, 99/788), depression (6.9%, 53/772), dementia (6.7%, 56/840), and atrial fibrillation (3.8%, 30/788). Undiagnosed diabetes mellitus and thyroid disease were rare (1%, 7/717 and 6/762, respectively). A median of 3 (interquartile range 1-8) activities of daily living were undertaken with difficulty. Overall, 77.6% (646/832) of participants rated their health compared with others of the same age as good, very good, or excellent. High contact rates in the previous year with general practitioners (93.8%, 960/1024) were recorded. Women had significantly higher disease counts (medians: women 5, men 4; P=0.033) and disability scores (medians: women 4, men 2; P=0.0006) than men, but were less likely to have attended outpatient clinics in the previous three months (women 29% (150/524), men 37% (118/320), odds ratio 0.7, 95% confidence interval 0.5 to 0.9).Conclusions This large cohort of 85 year olds showed good levels of both self rated health and functional ability despite significant levels of disease and impairment. Hypertension, ischaemic heart disease, atrial fibrillation, depression, and dementia may be underdiagnosed. Notable differences were found between the sexes: women outnumbered men and had more disease and disability.

Objective To assess the impairment in daily living activities in older people with age related changes in white matter according to the severity of these changes.Design Observational data collection and follow-up of a cohort of older people undergoing brain magnetic resonance imaging after non-disabling complaints.Setting 11 European centres.Participants 639 non-disabled older patients (mean age 74.1 (SD 5.0), 45.1% men) in whom brain magnetic resonance imaging showed mild, moderate, or severe age related changes in white matter (Fazekas scale). Magnetic resonance imaging assessment also included cerebral infarcts and atrophy.Main outcome measure Transition from no disability (defined as a score of 0 or 1 on the instrumental activities of daily living scale) to disability (score ≥2) or death over three year follow-up. Secondary outcomes were incident dementia and stroke.Results Over a mean follow-up period of 2.42 years (SD 0.97, median 2.94 years), information on the main outcome was available for 633 patients. The annual rate of transition or death was 10.5%, 15.1%, and 29.5%, respectively, for patients with mild, moderate, or severe age related changes in white matter (Kaplan-Meier log rank test P<0.001). In a Cox model comparing severe with mild changes and adjusted for clinical factors of functional decline, the risk of transition to disability or death was more than twofold higher (hazard ratio 2.36, 95% confidence interval 1.65 to 3.81). The other predictors were age group, history of atrial fibrillation, and complaint of gait disturbances. The effect of severe changes remained significant independently of baseline degree of atrophy and number of infarcts. Incident stroke and dementia only slightly modified this effect.Conclusion The three year results of the LADIS study suggest that in older adults who seek medical attention for non-disabling complaints, severe age related changes in white matter independently and strongly predict rapid global functional decline.

Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated.Design Prospective seven year cohort study.Setting General population, Montpellier, France.Participants 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1) years.Main outcome measures Diagnosis of mild cognitive impairment or dementia established by a standardised neurological examination.Results Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia. Mean percentage population attributable fractions were calculated with 95% confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia. The final model retained crystallised intelligence (population attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%), depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%, 0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E ε4 allele (7.11%, 2.44% to 11.98%).Conclusions Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia, outweighing even the effect of removing the principal known genetic risk factor. Although causal relations cannot be concluded with certainty, the study suggests priorities that may inform public health programmes.

Objective To identify common difficult decisions made by family carers on behalf of people with dementia, and facilitators of and barriers to such decisions, in order to produce information for family carers about overcoming barriers.Design Qualitative study to delineate decision areas through focus groups and complexity of decision making in individual interviews.Setting Community settings in London.Participants 43 family carers of people with dementia in focus groups and 46 carers who had already made such decisions in individual interviews.Results Family carers identified five core problematic areas of decision making: accessing dementia related health and social services; care homes; legal-financial matters; non-dementia related health care; and making plans for the person with dementia if the carer became too ill to care for them. They highlighted the difficulties in making proxy decisions, especially against active resistance, and their altered role of patient manager while still a family member. Families devised strategies to gain agreement in order to ensure that the person with dementia retained dignity.Conclusions The following strategies helped with implementation of decisions: introducing change slowly; organising legal changes for the carer as well as the patient; involving a professional to persuade the patient to accept services; and emphasising that services optimised, not impeded, independence. To access services, carers made patients’ general practice appointments, accompanied them to the surgery, pointed out symptoms, gained permission to receive confidential information, asked for referral to specialist services, and used professionals’ authority to gain patients’ agreement. End of life decisions were particularly difficult. They were helped by knowledge of the person with dementia’s previous views, clear prognostic information, and family support. Information sheets to help carers to overcome barriers to proxy decision making have been developed; their impact in practice has yet to be evaluated.

Objective To evaluate the association between use of benzodiazepines and incident dementia.Design Prospective, population based study.Setting PAQUID study, France.Participants 1063 men and women (mean age 78.2 years) who were free of dementia and did not start taking benzodiazepines until at least the third year of follow-up.Main outcome measures Incident dementia, confirmed by a neurologist.Results During a 15 year follow-up, 253 incident cases of dementia were confirmed. New use of benzodiazepines was associated with an increased risk of dementia (multivariable adjusted hazard ratio 1.60, 95% confidence interval 1.08 to 2.38). Sensitivity analysis considering the existence of depressive symptoms showed a similar association (hazard ratio 1.62, 1.08 to 2.43). A secondary analysis pooled cohorts of participants who started benzodiazepines during follow-up and evaluated the association with incident dementia. The pooled hazard ratio across the five cohorts of new benzodiazepine users was 1.46 (1.10 to 1.94). Results of a complementary nested case-control study showed that ever use of benzodiazepines was associated with an approximately 50% increase in the risk of dementia (adjusted odds ratio 1.55, 1.24 to 1.95) compared with never users. The results were similar in past users (odds ratio 1.56, 1.23 to 1.98) and recent users (1.48, 0.83 to 2.63) but reached significance only for past users.Conclusions In this prospective population based study, new use of benzodiazepines was associated with increased risk of dementia. The result was robust in pooled analyses across cohorts of new users of benzodiazepines throughout the study and in a complementary case-control study. Considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects of this drug class in the general population, indiscriminate widespread use should be cautioned against.

Objective To evaluate the effect of a video decision support tool on the preferences for future medical care in older people if they develop advanced dementia, and the stability of those preferences after six weeks. Design Randomised controlled trial conducted between 1 September 2007 and 30 May 2008. Setting Four primary care clinics (two geriatric and two adult medicine) affiliated with three academic medical centres in Boston. Participants Convenience sample of 200 older people (≥65 years) living in the community with previously scheduled appointments at one of the clinics. Mean age was 75 and 58% were women. Intervention Verbal narrative alone (n=106) or with a video decision support tool (n=94). Main outcome measures Preferred goal of care: life prolonging care (cardiopulmonary resuscitation, mechanical ventilation), limited care (admission to hospital, antibiotics, but not cardiopulmonary resuscitation), or comfort care (treatment only to relieve symptoms). Preferences after six weeks. The principal category for analysis was the difference in proportions of participants in each group who preferred comfort care. Results Among participants receiving the verbal narrative alone, 68 (64%) chose comfort care, 20 (19%) chose limited care, 15 (14%) chose life prolonging care, and three (3%) were uncertain. In the video group, 81 (86%) chose comfort care, eight (9%) chose limited care, four (4%) chose life prolonging care, and one (1%) was uncertain (χ2=13.0, df=3, P=0.003). Among all participants the factors associated with a greater likelihood of opting for comfort care were being a college graduate or higher, good or better health status, greater health literacy, white race, and randomisation to the video arm. In multivariable analysis, participants in the video group were more likely to prefer comfort care than those in the verbal group (adjusted odds ratio 3.9, 95% confidence interval 1.8 to 8.6). Participants were re-interviewed after six weeks. Among the 94/106 (89%) participants re-interviewed in the verbal group, 27 (29%) changed their preferences (κ=0.35). Among the 84/94 (89%) participants re-interviewed in the video group, five (6%) changed their preferences (κ=0.79) (P<0.001 for difference). Conclusion Older people who view a video depiction of a patient with advanced dementia after hearing a verbal description of the condition are more likely to opt for comfort as their goal of care compared with those who solely listen to a verbal description. They also have more stable preferences over time. Trial registration Clinicaltrials.gov NCT00704886.