Quantification of adaptive forces on SNP rs1010211 due to viral zoonotic pathogens.

Widespread genotyping of human populations in environmental homeostasis has created opportunities to quantify how environmental parameters affect the genomic distribution of variants in healthy populations. This represents an ongoing natural experiment upon the human species that can only be understood through developing models of adaptation. By examining the information dynamics of optimal SNP distributions within such populations, "adaptive forces" on genomic variants can be quantified through comparisons between different populations. To this end, we are performing double-blind scans of SNPs in order to ascertain any potential smooth functional relationships between the frequencies of the variants and changes in quantified environmental parameters. At present, we have sequentially examined more than twenty thousand SNPs (on chromosome 3) of nine homeostatic native populations for potential adaptive flagging of the variants as functions of 15 environmental parameters. Our first significant flag has related rs1010211 to viral pathogens in mammalian hosts. Such pathogens present a significant risk for the emergence of new infectious diseases in humans. This genomic variant is within the gene TNIK, which is a germinal center kinase (GCK). GCKs are participants in both adaptive and innate immune regulation. However, the function of TNIK is not fully understood. We quantify the adaptive force on the C allele due to the pathogens as 0.04 GEU's/viral species.

Predictive Factors for Conversion to Dementia in Individuals with Early-Onset Mild Cognitive Impairment.

INTRODUCTION: There is little research on factors predicting conversion to dementia in early-onset mild cognitive impairment (eoMCI), a transitional stage between healthy ageing and dementia in individuals below the age of 65. We aimed to examine whether sociodemographic and clinical factors at initial presentation predicted dementia progression in a cohort of eoMCI patients attending a memory service, at a university teaching hospital in the UK. METHODS: This is a retrospective case note study of individuals diagnosed with eoMCI between 2000 and 2013 at the Younger Person's Memory Service (YPMS) in Leicestershire, England. Data collected at assessment included social factors, demographic characteristics, and medical and psychiatric history, as well as standardized cognitive assessment scores. Variables were analysed using χ2 or independent sample t tests to identify associations. A Cox regression survival analysis was done to identify predictive factors for dementia conversion. An ROC analysis for total CAMCOG was used to investigate sensitivity and specificity for dementia converters versus non-converters. RESULTS: Out of 531 subjects who attended YPMS, 65 patients were given a diagnosis of eoMCI (47.7% female; mean age 56.4 ± 7.54 years). Of these, 21 (32.3%) converted to dementia during their course within the service. Comparison between subgroups revealed a significant association between dementia conversion and higher years of education and lower MMSE and CAMCOG (total and subscale) scores at baseline. Smoking history, alcohol use, or medical history such as diabetes or heart disease were not associated with conversion. Cox regression survival analysis showed higher education in years and lower total CAMCOG scores were significant predictors for conversion. Lower scores on the recent memory, remote memory, learning memory, and executive function subscales of the CAMCOG were also significant predictors for conversion. ROC curve analysis for total CAMCOG demonstrated that the best detection of dementia converters can be achieved with a cutoff score of 90.5/107 (sensitivity of 76.2% and specificity of 68.2%). Area under the curve was 0.808 (95% CI: 0.697-0.920). CONCLUSION: More years in education and lower cognitive scores on CAMCOG at initial assessment are associated with progression to dementia from eoMCI. Further research is required to explore these predictive factors more.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Screening for depression in older people on acute medical wards: the validity of the Edinburgh Depression Scale.

BACKGROUND: depression is common in people with poor physical health, particularly within the acute medical in-patient setting. Co-morbid depression contributes to poor outcomes, and screening for depression in acute medical in-patients has been advocated. The Edinburgh Depression Scale (EDS) has been validated in a variety of general hospital patient groups, but not previously in older acute medical in-patients. METHODS: one hundred and eighteen patients aged 65 and older on acute medical wards were assessed using a standardised diagnostic interview (Present State Examination-Schedules for Clinical Assessment in Neuropsychiatry) to identify depression according to ICD-10 criteria. They subsequently completed the EDS. The performance characteristics at a range of thresholds were compared, and receiver operating characteristic curve analysis was performed. RESULTS: the optimal EDS cut-off for identifying ICD-10 depressive episode was 7/8, with a sensitivity of 88%, specificity of 77%, positive predictive value of 52% and negative predictive value of 96%. The area under the receiver operating characteristic curve was 0.91. CONCLUSION: the EDS was shown to be a useful instrument for detecting clinical depression in older people on acute medical wards in this study. Its performance was equivalent to other validated screening instruments in this population. Our findings add further weight to using the EDS as a screening instrument for depression in multiple general hospital settings.

Donepezil and memantine for moderate-to-severe Alzheimer's disease.

BACKGROUND: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. METHODS: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS: Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone. CONCLUSIONS: In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.).

Screening for depression in older adults on an acute medical ward: the validity of NICE guidance in using two questions.

BACKGROUND: depression is common in older people in general hospital settings and associated with poor outcomes. This study aimed to evaluate the validity of two screening questions recommended by the UK National Institute for Health and Clinical Excellence (NICE). METHODS: one hundred and eighteen patients aged over 65 years, admitted to acute medical wards at a teaching hospital, were interviewed in a standardised manner using relevant sections of the Present State Examination-Schedules for Clinical Assessment in Neuropsychiatry to identify depression according to ICD-10 criteria. Subsequently, participants completed the two depression screening questions and the 15-item version of the Geriatric Depression Scale (GDS-15). RESULTS: a threshold of one or more positive responses to the two NICE depression screening questions gave a sensitivity of 100%, specificity of 71%, positive predictive value (PPV) of 49% and negative predictive value (NPV) of 100%. The GDS-15 optimal cut-off was 6/7 with a sensitivity of 80%, specificity of 86%, PPV of 62% and NPV of 94%. A two-stage screening process utilising the NICE two questions followed by the GDS-15 with these cut-offs gave a sensitivity of 80%, specificity of 91%, PPV of 71% and NPV of 94%. CONCLUSION: the two depression questions perform well as an initial screening process for non-cognitively impaired older people in the acute medical setting. A positive response to either question would indicate that further assessment is required by a clinician competent in diagnosing depression in this population, or the possible use of a more detailed instrument such as the GDS-15 to reduce the number of false-positive cases.

The utility of the Edinburgh Depression Scale as a screening tool for depression in Parkinson's disease.

OBJECTIVE: This study aimed to evaluate the Edinburgh Depression Scale (EDS) as a screening tool for use in a Parkinson's disease (PD) population. Many commonly used depression scales include items relating to somatic symptoms that also occur in PD, which could potentially result in inaccurate reporting of depressive symptoms. The EDS is a scale that incorporates no somatic items. METHOD: One hundred twenty patients attending specialist PD clinics were assessed using a standardised diagnostic interview (Present State Examination--Schedules for Clinical Assessment in Neuropsychiatry) to establish a diagnosis of DSM-IV depression. They later completed the EDS with another researcher who was blind to the results of diagnostic interview. A receiver operating characteristic curve analysis was carried out to identify the optimal threshold score on the EDS and the Brief EDS to identify any depressive disorder or major depression. The performance characteristics at a range of thresholds were compared. RESULTS: A cut-off score of 10/11 gave maximal discriminant validity, with 74% sensitivity, 92% specificity and 64% positive predictive value for the identification of any depression according to DSM-IV criteria. CONCLUSIONS: This study suggests that the EDS is both a valid and potentially useful instrument that can be used as a quick self-completion questionnaire for screening for depression in people who have PD.

Screening for depression in Parkinson's disease: the performance of two screening questions.

BACKGROUND: the study objective was to evaluate the validity of the two questions recommended by the UK. National Institute for Health and Clinical Excellence for depression screening in Parkinson's disease (PD). METHODS: one hundred and twenty patients attending a PD out-patient clinic were interviewed in a standardised manner using relevant sections of the Present State Examination- Schedules for Clinical Assessment in Neuropsychiatry to identify depression according to Diagnostic and Statistical Manual (4th edition) criteria. Participants then completed the two depression screening questions and the 15-item Geriatric Depression Scale (GDS-15). RESULTS: sensitivity, specificity, positive and negative predictive values of the two questions and GDS-15 for major and minor depression combined were calculated for different cut-off scores and a receiver operating characteristics (ROC) analysis was conducted. A threshold of one or more positive responses to the two screening questions gave a sensitivity of 100% and specificity of 84% (positive predictive value 54%, negative predictive value 100%). The area under the ROC curve was 0.95. The optimal cut-off for the GDS-15 was 5/6, which gave a sensitivity of 84% and specificity of 89% (positive predictive value 59%, negative predictive value 97%), and the area under the curve was 0.92. CONCLUSION: this study shows that the two depression screening questions can be used as an initial screen for depression in patients with PD who have no significant cognitive impairment. A positive response to either of the questions would indicate that further diagnostic assessment may be warranted.

Review of brief cognitive tests for patients with suspected dementia.

BACKGROUND: As the population ages, it is increasingly important to use effective short cognitive tests for suspected dementia. We aimed to review systematically brief cognitive tests for suspected dementia and report on their validation in different settings, to help clinicians choose rapid and appropriate tests. METHODS: Electronic search for face-to-face sensitive and specific cognitive tests for people with suspected dementia, taking ≤ 20 minutes, providing quantitative psychometric data. RESULTS: 22 tests fitted criteria. Mini-Mental State Examination (MMSE) and Hopkins Verbal Learning Test (HVLT) had good psychometric properties in primary care. In the secondary care settings, MMSE has considerable data but lacks sensitivity. 6-Item Cognitive Impairment Test (6CIT), Brief Alzheimer's Screen, HVLT, and 7 Minute Screen have good properties for detecting dementia but need further validation. Addenbrooke's Cognitive Examination (ACE) and Montreal Cognitive Assessment are effective to detect dementia with Parkinson's disease and Addenbrooke's Cognitive Examination-Revised (ACE-R) is useful for all dementias when shorter tests are inconclusive. Rowland Universal Dementia Assessment scale (RUDAS) is useful when literacy is low. Tests such as Test for Early Detection of Dementia, Test Your Memory, Cognitive Assessment Screening Test (CAST) and the recently developed ACE-III show promise but need validation in different settings, populations, and dementia subtypes. Validation of tests such as 6CIT, Abbreviated Mental Test is also needed for dementia screening in acute hospital settings. CONCLUSIONS: Practitioners should use tests as appropriate to the setting and individual patient. More validation of available tests is needed rather than development of new ones.

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial.

BACKGROUND: Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS: To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD: A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS: There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS: In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.

Evidence of cancer-linked rodent zoonoses from biophysical genomic variations.

As a mechanism to explore the role of environmental adaptation in establishing the optimal distribution of single nucleotide polymophisms (SNPs) within resident homeostatic populations, relationships between quantified environmental parameters and the frequencies of the variants are being explored. We have performed sequential double-blind scans on more than 30% of chromosome 3 in an attempt to discover possible relationships using simple mathematical functions that are indicative of "adaptive forces" on the variants due to specific quantified environmental agents. We have found an association of rs13071758 with rodent zoonotic diseases. This variant is within the FHIT gene, which spans the most fragile of the common fragile sites in human lymphoblasts. FHIT, which is highly sensitive to environmental carcinogens, is partially lost in most human cancers. This finding is consistent with other studies postulating an association between rodent zoonoses and cancer. We quantify the adaptive force on the T allele as 0.28 GEUs per unit of zoonotic rodent host richness.

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.

BACKGROUND: Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo. METHODS: We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at King's College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38. FINDINGS: Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1·17, 95% CI -0·23 to 2·58; p=0·10) or mirtazapine (0·01, -1·37 to 1·38; p=0·99), or between participants in the mirtazapine and sertraline groups (1·16, -0·25 to 2·57; p=0·11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0·010) or mirtazapine group (44 of 108, 41%; p=0·031), and fewer serious adverse events rated as severe (p=0·003). Five patients in every group died by week 39. INTERPRETATION: Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer's disease should be reconsidered. FUNDING: UK National Institute of Health Research HTA Programme.

Determining the minimum clinically important differences for outcomes in the DOMINO trial.

BACKGROUND: Although less likely to be reported in clinical trials than expressions of the statistical significance of differences in outcomes, whether or not a treatment has delivered a specified minimum clinically important difference (MCID) is also relevant to patients and their caregivers and doctors. Many dementia treatment randomised controlled trials (RCTs) have not reported MCIDs and, where they have been done, observed differences have not reached these. METHODS: As part of the development of the Statistical Analysis Plan for the DOMINO trial, investigators met to consider expert opinion- and distribution-based values for the MCID and triangulated these to provide appropriate values for three outcome measures, the Standardised Mini-mental State Examination (sMMSE), Bristol Activities of Daily Living Scale (BADLS) and Neuropsychiatric Inventory (NPI). Only standard deviations (SD) were presented to investigators who remained blind to treatment allocation. RESULTS: Adoption of values for MCIDs based upon 0.4 of the SD of the change in score from baseline on the sMMSE, BADLS and NPI in the first 127 participants to complete DOMINO yielded MCIDs of 1.4 points for sMMSE, 3.5 for BADLS and 8.0 for NPI. CONCLUSIONS: Reference to MCIDs is important for the full interpretation of the results of dementia trials and those conducting such trials should be open about the way in which they have determined and chosen their values for the MCIDs.

The meaning of reporting forgetfulness: a cross-sectional study of adults in the English 2007 Adult Psychiatric Morbidity Survey.

OBJECTIVES: we measured subjective memory impairment (SMI) across the whole adult age range in a representative, national survey. Age is the strongest risk factor for dementia and SMI may be a precursor of objective cognitive impairment. We therefore hypothesised that SMI prevalence would rise with age in a non-demented population. METHOD: we analysed data from the English 2007 Adult Psychiatric Morbidity Survey, representative of people in private households. Participants were asked whether they had noticed problems with forgetting in the last month, or forgotten anything important in the last week; and completed the modified Telephone Interview for Cognitive Status. RESULTS: of those contacted, 7,461 (57%) participated. After excluding participants screening positive for dementia, 2,168 (31.7%) reported forgetfulness in the last month, while 449 (6.4%) had forgotten something important in the last week. Reporting forgetfulness was not associated with age. In a multivariate analysis including cognition and age, the only significant associates of reporting forgetfulness were anxiety, depressive and somatic symptoms. CONCLUSIONS: our hypothesis that subjective forgetfulness prevalence would rise with age in a non-demented population was not supported. Although subjective forgetfulness can be an early symptom of future or mild dementia, it is common and non-specific and-at population level-is more likely to be related to mood than to be an early symptom of dementia. Asking those presenting with subjective forgetfulness additional questions about memory and functional decline and objective forgetfulness is likely to help clinicians to detect those at risk of dementia.

Suicides by country of birth groupings in England and Wales: age-associated trends and standardised mortality ratios.

INTRODUCTION: Suicide rates in England and Wales have declined in recent years. A better understanding of age-associated trends in different ethnic groups may inform strategies to sustain this decline. MATERIALS AND METHODS: This study examines suicide rates and age-associated trends in England and Wales by country of birth (used as a proxy for ethnicity) using the latest available national mortality data. RESULTS: The main findings were (a) suicide rates were generally higher in males than females in all age bands in all country of birth groups except the China group, where suicides rates were higher in females than males in the older age bands; (b) male suicide rates increased with ageing in the Indian sub-continent group and female suicide rates increased with ageing in the Africa and China groups; (c) male standardised mortality ratios (SMRs) were generally higher in the younger age bands in the Eastern Europe and Caribbean groups and generally lower in the Australasian, Middle East and Western Europe groups; (d) male SMRs were generally higher in the older age bands in Eastern Europe, Caribbean, Australasian and Western Europe groups and lower in all age bands in the Indian sub-continent group, and (e) female SMRs were generally higher in the older age bands in the China, Africa and Caribbean groups. CONCLUSION: There is a need for epidemiological data on suicides in BME groups, including age-associated trends, trends over time, risk and protective factors and methods of suicide to inform suicide prevention strategies.

Donepezil for the treatment of agitation in Alzheimer's disease.

BACKGROUND: Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear. METHODS: We randomly assigned 272 patients with Alzheimer's disease who had clinically significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day (128 patients) or placebo (131 patients) for 12 weeks. The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory (CMAI) (on a scale of 29 to 203, with higher scores indicating more agitation) at 12 weeks. RESULTS: There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks (estimated mean difference in change [the value for donepezil minus that for placebo], -0.06; 95% confidence interval [CI], -4.35 to 4.22). Twenty-two of 108 patients (20.4%) in the placebo group and 22 of 113 (19.5%) in the donepezil group had a reduction of 30% or greater in the CMAI score (the value for donepezil minus that for placebo, -0.9 percentage point; 95% CI, -11.4 to 9.6). There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory, the Neuropsychiatric Inventory Caregiver Distress Scale, or the Clinician's Global Impression of Change. CONCLUSIONS: In this 12-week trial, donepezil was not more effective than placebo in treating agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00142324 [ClinicalTrials.gov].).

Predictors of Disease Progression in Early-Onset Alzheimer's Dementia: A Retrospective Cohort Study.

OBJECTIVES: Early-onset Alzheimer's disease (EOAD), defined as onset of AD before the age of 65 years, is less common than the late-onset type, and little is known about the factors affecting disease progression. The aim of the study was to investigate factors influencing disease progression in people with EOAD. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: People with EOAD who were assessed and attended the specialist memory service at a university teaching hospital in a European setting, between 2000 and 2010. MEASURES: Sociodemographic details and clinical and cognitive assessments at initial assessment were used as potential predictors of change in clinical status and outcome at final follow-up within the memory service. RESULTS: Of the 101 people diagnosed with EOAD during this period, 96 patients were followed up (53 women; aged 59 ± 4.9 years; mean follow-up 36.3 ± 29.12 months). Patients were classified as Stable (n = 25) if continued within the memory service or discharged to primary care, and those transferred to other specialist services (n = 66) for further inputs, institutional care (n = 4), or died (n = 1) were classified as Worseners (n = 71). Lower education (P = .008), lower Cambridge Cognition Examination scores (P = .049), and presence of family history of dementia [P = .012, χ2 (1) = 8.84] was associated with worse change in clinical status. Furthermore, cognitive deficits such as lower scores on comprehension, recent memory, and executive functions were found to predict a worse clinical outcome. CONCLUSIONS AND IMPLICATIONS: Identification of predictors of faster disease progression has significant clinical benefit, allowing clinicians to estimate prognosis and plan patient care accordingly.

Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial).

BACKGROUND: Good practice guidelines state that a psychological intervention should usually precede pharmacotherapy, but there are no data evaluating the feasibility of psychological interventions used in this way. METHODS: At the first stage of a randomized blinded placebo-controlled trial, 318 patients with Alzheimer disease (AD) with clinically significant agitated behavior were treated in an open design with a psychological intervention (brief psychosocial therapy [BPST]) for 4 weeks, preceding randomization to pharmacotherapy. The therapy involved social interaction, personalized music, or removal of environmental triggers. RESULTS: Overall, 318 patients with AD completed BPST with an improvement of 5.6 points on the total Cohen-Mansfield Agitation Inventory (CMAI; mean [SD], 63.3 [16.0] to 57.7 [18.4], t = 4.8, df = 317, p < 0.0001). Therapy worksheets were completed in six of the eight centers, with the key elements of the intervention delivered according to the manual for >95% of patients. More detailed evaluation of outcome was completed for the 198 patients with AD from these centers, who experienced a mean improvement of 6.6 points on the total CMAI (mean [SD], 62.2 [14.3] to 55.6 [15.8], t = 6.5, df = 197, p < 0.0001). Overall, 43% of participants achieved a 30% improvement in their level of agitation. CONCLUSION: The specific attributable benefits of BPST cannot be determined from an open trial. However, the BPST therapy was feasible and was successfully delivered according to an operationalized manual. The encouraging outcome indicates the need for a randomized controlled trial of BPST.

Comparison of elderly suicide rates among migrants in England and Wales with their country of origin.

BACKGROUND: The black and minority ethnic (BME) elderly population size in England and Wales has progressively increased over the last three decades. Only two studies, both well over a decade old, have compared suicide rates in BME groups in England and Wales with those in their country of origin. METHODS: A study comparing suicide rates among elderly migrants in England and Wales and in their country of origin using the latest available mortality data from the Office of National Statistics and the World Health Organization was conducted. RESULTS: There were wide variations in standardised mortality ratios for elderly suicides among migrants from different countries compared with those born in England and Wales and in their country of origin. There was convergence towards elderly suicide rates for England and Wales in some migrant groups in males in the age-bands 65-74 years and 75 + years, and in females in the age-band 75 + years. However, males aged 75 + years from most migrant groups had higher rates than those born in England and Wales. CONCLUSION: A more detailed analysis of suicide of older people from migrant groups is required to determine vulnerability and protective influences.

Cognitive function and common mental disorders in older people with vascular and non-vascular disorders: a national survey.

OBJECTIVE: Vascular disorders are important potential causes of cognitive impairment and common mental disorders but their specificity as risk factors has yet to be clarified. The objectives of this analysis were to compare vascular and non-vascular health problems with respect to their associations with cognitive function and common mental disorder. METHOD: An analysis was carried out of cross-sectional data from the 2000 UK National Survey of Psychiatric Morbidity. The two dependent variables analysed were common mental disorder (revised Clinical Interview Schedule) and cognitive function (TICSm and animal naming) in survey participants who were aged 60-74 years (n = 2007). Associations with self-reported vascular and common non-vascular (musculoskeletal, respiratory or gastrointestinal) disorders were compared. Disability (SF-12 physical scale) was considered as a potential confounding/mediating factor). RESULTS: Vascular disorders were associated with impaired global cognitive function and lower memory but not verbal fluency scores after adjustment for age, gender, education and social class. No such associations were found for non-vascular disorders. Vascular and non-vascular disorders were associated with common mental disorder to a similar extent, and associations were substantially explained by disability. CONCLUSIONS: Lower cognitive function was specifically associated with vascular disorders. Findings for common mental disorder were more consistent with an effect of disability rather than the actual consequences of specific health complaints.