Eric P. Moll van Charante

Prevention of dementia by intensive vascular care (PreDIVA): a cluster-randomized trial in progress.

Background and PurposeCardiovascular risk factors are associated with an increased risk of dementia. Treatment of hypertension and hypercholesterolemia is associated with a decrease in incident dementia. Whether interventions aimed at cardiovascular risk factors in late life also reduce dementia risk is unknown. Here, we report the outline of a pragmatic study that will attempt to answer this question and we describe the prevalence of cardiovascular risk factors in the target population. MethodsWe designed a large cluster-randomized trial with a 6-year follow-up in 3700 elderly subjects (70 to 78 y) to assess whether nurse-led intensive vascular care in primary care decreases the incidence of dementia and reduces disability. Secondary outcome parameters are mortality, incidence of vascular events, and cognitive functioning. Intensive vascular care comprises treatment of hypertension, hypercholesterolemia, diabetes and reducing overweight, smoking cessation, and stimulating physical exercise. ResultsBaseline data of 1004 subjects show that 87% of the subjects have 1 or more cardiovascular risk factors and 44% have even 2 or more risk factors amenable to treatment. Seventy-nine percent of the subjects receiving antihypertensive medication still have a systolic pressure of >140 mm Hg. ConclusionsIn this older age group, the very high percentage of elderly subjects with cardiovascular risk factors illustrates the large window of opportunity for therapies directed to lower the cardiovascular risk and potentially also the risk for dementia.

Apathy in Parkinson's disease: A systematic review and meta-analysis

Apathy is a frequently reported neuropsychiatric symptom in Parkinsons disease (PD), but its prevalence and clinical correlates are debated. We aimed to address these issues by conducting a systematic review and meta‐analysis. Embase, Medline/PubMed, and PsychINFO databases were searched for relevant studies. Data were extracted by two independent observers, using predefined extraction forms tailored specifically to the research question. From 1,702 titles and abstracts, 23 studies were selected. Meta‐analysis showed a prevalence of apathy in PD of 39.8% (n = 5,388, 905% CI 34.6‐45.0%). Apathy was associated with higher age (3.3 years, 95% CI = 1.7‐4.9), lower mean Mini‐Mental State Evaluation (MMSE) score (−1.4 points, 95% CI = −2.1 to −0.8), an increased risk of co‐morbid depression (relative risk [RR] = 2.3, 95% CI = 1.9‐2.8), higher Unified Parkinsons Disease Rating Scale (UPDRS) motor score (6.5 points, 95% CI = 2.6‐10.3), and more severe disability (Hedges‐G = 0.5, 95% CI = 0.3‐0.6). Half of the patients with apathy had concomitant depression (57.2%, 95% CI = 49.4‐64.9%), and this estimate was similar after exclusion of patients with cognitive impairment (52.5%, 95% CI = 42.2%‐62.8%). In conclusion, we found that apathy affects almost 40% of patients with PD. Several factors influence reported prevalence rates, contributing to the considerable heterogeneity in study results. Half of patients with apathy do not suffer from concomitant depression or cognitive impairment, confirming its status as a separate clinical syndrome in PD. The pervasiveness of apathy in PD warrants research into its treatment, although different underlying pathophysiological mechanisms may require different treatment strategies. Treatment of apathy could improve patient quality of life, reduce caregiver burden, alleviate disability by increasing motivation for self‐care, and reduce cognitive impairment by improving executive functioning.

Effectiveness of a 6-year multidomain vascular care intervention to prevent dementia (preDIVA): a cluster-randomised controlled trial

BACKGROUND Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a population of community-dwelling older people. METHODS In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70-78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score [ALDS]) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771. FINDINGS Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6·7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio [HR] 0·92, 95% CI 0·71-1·19; p=0·54). Mean ALDS scores measured during follow-up did not differ between groups (85·7 [SD 6·8] in the intervention group and 85·7 [7·1] in the control group; adjusted mean difference -0·02, 95% CI -0·38 to 0·42; p=0·93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0·98, 95% CI 0·80-1·18; p=0·81). Incident cardiovascular disease did not differ between groups (273 [19%] of 1469 participants in the intervention group and 228 [17%] of 1307 participants in the control group; HR 1·06, 95% CI 0·86-1·31; p=0·57). INTERPRETATION A nurse-led, multidomain intervention did not result in a reduced incidence of all-cause dementia in an unselected population of older people. This absence of effect might have been caused by modest baseline cardiovascular risks and high standards of usual care. Future studies should assess the efficacy of such interventions in selected populations. FUNDING Dutch Ministry of Health, Welfare and Sport; Dutch Innovation Fund of Collaborative Health Insurances; and Netherlands Organisation for Health Research and Development.

Treatment of cardiovascular risk factors to prevent cognitive decline and dementia: a systematic review

Background: Over the last decade, evidence has accumulated that vascular risk factors increase the risk of Alzheimer disease (AD). So far, few randomized controlled trials have focused on lowering the vascular risk profile to prevent or postpone cognitive decline or dementia. Objective: To systematically perform a review of randomized controlled trials (RCTs) evaluating drug treatment effects for cardiovascular risk factors on the incidence of dementia or cognitive decline. Selection criteria: RCTs studying the effect of treating hypertension, dyslipidemia, hyperhomocysteinemia, obesity, or diabetes mellitus (DM) on cognitive decline or dementia, with a minimum follow-up of 1 year in elderly populations. Outcome measure: Cognitive decline or incident dementia. Main results: In the identified studies, dementia was never the primary outcome. Statins (2 studies) and intensified control of type II DM (1 study) appear to have no effect on prevention of cognitive decline. Studies on treatment of obesity are lacking, and the results of lowering homocysteine (6 studies) are inconclusive. There is some evidence of a preventive effect of antihypertensive medication (6 studies), but results are inconsistent. Conclusion: The evidence of a preventive treatment effect aimed at vascular risk factors on cognitive decline and dementia in later life is scarce and mostly based on secondary outcome parameters. Several important sources of bias such as differential dropout may importantly affect interpretation of trial results.

Out-of-hours demand for GP care and emergency services: patients' choices and referrals by general practitioners and ambulance services

BackgroundOver the last five years, Dutch provision of out-of-hours primary health care has shifted from practice-based services towards large-scale general practitioner (GP) cooperatives. Only few population-based studies have been performed to assess the out-of-hours demand for GP and emergency care, including the referral patterns to the Accident and Emergency Department (AED) by GPs and ambulance services.MethodDuring two four-month periods (five-year interval), a prospective cross-sectional study was performed for a Dutch population of 62,000 people. Data were collected on all patient contacts with one GP cooperative and three AEDs bordering the region.ResultsOverall, GPs handled 88% of all out-of-hours contacts (275/1000 inhabitants/year), while the AED dealt with the remaining 12% of contacts (38/1000 inhabitants/year). Within the AED, the self-referrals represented a substantial number of contacts (43%), although within the total out-of-hours demand they only represented 5% of all contacts. Self-referrals were predominantly young adult males presenting with an injury, nineteen percent of whom had a fracture. Compared to self-referrals, patients who were referred by the GP or brought in by the ambulance services were generally older and were more frequently admitted for both injury and non-injury (p < 0.01 for all differences).ConclusionThe GP cooperative deals with the large majority of out-of-hours problems presented. Within the total demand, self-referrals constitute a stable, yet small group of patients, many of whom seem to have made a reasonable choice to attend the AED. The GPs and the ambulance services appear to be effectively selecting the problems that are presented to the AED.

Association of Vascular Factors With Apathy in Community-Dwelling Elderly Individuals

CONTEXT Apathy in community-dwelling elderly individuals has been associated with a history of stroke and other cardiovascular disease. OBJECTIVE To assess the relationship between symptoms of apathy and cardiovascular risk factors or disease (stroke or other) in a large sample of elderly people aged 70 to 78 years without depression or dementia. DESIGN Cross-sectional data analysis within an ongoing cluster-randomized, open, multicenter trial. SETTING The Netherlands, general community. PARTICIPANTS We studied 3534 elderly individuals without dementia who were included in the Prevention of Dementia by Intensive Vascular Care trial. MAIN OUTCOME MEASURES Symptoms of apathy, assessed with 3 items from the 15-item Geriatric Depression Scale, in participants with few or no depressive symptoms. RESULTS The median age of participants was 74.3 years. Principal components analysis of the Geriatric Depression Scale confirmed a separate factor for the apathy items (Geriatric Depression Scale-3A). Two or more symptoms of apathy were present in 699 participants (19.9%), of whom 372 (53.2%) were without depressive symptoms (Geriatric Depression Scale-12D score <2). Ordinal regression analysis showed that increasing apathy in the absence of depressive symptoms was associated with a history of stroke (odds ratio, 1.79; 95% CI, 1.38-2.31) and cardiovascular disease other than stroke (1.28; 1.09-1.52). Exploratory analysis among 1889 participants free from stroke and other cardiovascular disease revealed an association between apathy score and the following cardiovascular risk factors: systolic blood pressure (P = .03), body mass index (P = .002), type 2 diabetes mellitus (P = .07), and C-reactive protein (P < .001). CONCLUSIONS Symptoms indicative of apathy are common in community-dwelling nondemented older people who are free from depression. The independent association of stroke, other cardiovascular disease, and cardiovascular risk factors with symptoms of apathy suggests a causal role of vascular factors.

Nurse telephone triage in out-of-hours GP practice: determinants of independent advice and return consultation

BackgroundNowadays, nurses play a central role in telephone triage in Dutch out-of-hours primary care. The percentage of calls that is handled through nurse telephone advice alone (NTAA) appears to vary substantially between GP cooperatives. This study aims to explore which determinants are associated with NTAA and with subsequent return consultations to the GP.MethodsFor the ten most frequently presented problems, a two-week follow-up cohort study took place in one cooperative run by 25 GPs and 8 nurses, serving a population of 62,291 people. Random effects logistic regression analysis was used to study the determinants of NTAA and return consultation rates. The effect of NTAA on hospital referral rates was also studied as a proxy for severity of illness.ResultsThe mean NTAA rate was 27.5% – ranging from 15.5% to 39.4% for the eight nurses. It was higher during the night (RR 1.63, CI 1.48–1.76) and lower with increasing age (RR 0.96, CI 0.93–0.99, per ten years) or when the patient presented >2 problems (RR 0.65; CI 0.51–0.83). Using cough as reference category, NTAA was highest for earache (RR 1.49; CI 1.18–1.78) and lowest for chest pain (RR 0.18; CI 0.06–0.47). After correction for differences in case mix, significant variation in NTAA between nurses remained (p < 0.001). Return consultations after NTAA were higher after nightly calls (RR 1.23; CI 1.04–1.40). During first return consultations, the hospital referral rate after NTAA was 1.5% versus 3.8% for non-NTAA (difference -2.2%; CI -4.0 to -0.5).ConclusionImportant inter-nurse variability may indicate differences in perception on tasks and/or differences in skill to handle telephone calls alone. Future research should focus more on modifiable determinants of NTAA rates.

Women with symptoms of uncomplicated urinary tract infection are often willing to delay antibiotic treatment: a prospective cohort study

BackgroundWomen presenting with symptoms of acute uncomplicated urinary tract infection (UTI) are often prescribed antibiotics. However, in 25 to 50% of symptomatic women not taking antibiotics, symptoms recover spontaneously within one week. It is not known how many women are prepared to delay antibiotic treatment. We investigated how many women presenting with UTI symptoms were willing to delay antibiotic treatment when asked by their general practitioner (GP).MethodsFrom 18 April 2006 until 8 October 2008, in a prospective cohort study, patients were recruited in 20 GP practices in and around Amsterdam, the Netherlands. Healthy, non-pregnant women who contacted their GP with painful and/or frequent micturition for no longer than seven days registered their symptoms and collected urine for urinalysis and culture. GPs were requested to ask all patients if they were willing to delay antibiotic treatment, without knowing the result of the culture at that moment. After seven days, patients reported whether their symptoms had improved and whether they had used any antibiotics.ResultsOf 176 women, 137 were asked by their GP to delay antibiotic treatment, of whom 37% (51/137) were willing to delay. After one week, 55% (28/51) of delaying women had not used antibiotics, of whom 71% (20/28) reported clinical improvement or cure. None of the participating women developed pyelonephritis.ConclusionsMore than a third of women with UTI symptoms are willing to delay antibiotic treatment when asked by their GP. The majority of delaying women report spontaneous symptom improvement after one week.

Preferences regarding disclosure of a diagnosis of dementia: a systematic review

Background: Studies in memory clinics suggest that the majority of patients would like to know of a diagnosis of dementia. It is less clear what preferences are in the community. Our objective was to review the literature on preferences regarding disclosure of a diagnosis of dementia and to assess key arguments in favor of and against disclosure. Methods: Systematic search of empirical studies was performed in Pubmed, Embase, and Psycinfo. We extracted preferences of individuals without cognitive impairment (general population; relatives of dementia patients; and physicians) and preferences of individuals referred to a memory clinic or already diagnosed with dementia. A meta-analysis was done using a random effects model. Our main conclusions are based on studies with a response rate ???75{\%}. Results: We included 23 articles (9.065 respondents). In studies with individuals without cognitive impairment, the pooled percentage in favor of disclosure was 90.7{\%} (95{\%}CI: 83.8{\%}-97.5{\%}). In studies with patients who were referred to a memory clinic or already diagnosed with dementia, the pooled percentage that considered disclosure favorable was 84.8{\%} (95{\%}CI: 75.6{\%}-94.0{\%}). The central arguments in favor of disclosure pertained to autonomy and the possibility to plan ones future. Arguments against disclosure were fear of getting upset and that knowing has no use. Conclusions: The vast majority of individuals without and with cognitive impairment prefers to be informed about a diagnosis of dementia for reasons pertaining to autonomy.BACKGROUND Studies in memory clinics suggest that the majority of patients would like to know of a diagnosis of dementia. It is less clear what preferences are in the community. Our objective was to review the literature on preferences regarding disclosure of a diagnosis of dementia and to assess key arguments in favor of and against disclosure. METHODS Systematic search of empirical studies was performed in Pubmed, Embase, and Psycinfo. We extracted preferences of individuals without cognitive impairment (general population; relatives of dementia patients; and physicians) and preferences of individuals referred to a memory clinic or already diagnosed with dementia. A meta-analysis was done using a random effects model. Our main conclusions are based on studies with a response rate ≥75%. RESULTS We included 23 articles (9.065 respondents). In studies with individuals without cognitive impairment, the pooled percentage in favor of disclosure was 90.7% (95%CI: 83.8%-97.5%). In studies with patients who were referred to a memory clinic or already diagnosed with dementia, the pooled percentage that considered disclosure favorable was 84.8% (95%CI: 75.6%-94.0%). The central arguments in favor of disclosure pertained to autonomy and the possibility to plan ones future. Arguments against disclosure were fear of getting upset and that knowing has no use. CONCLUSIONS The vast majority of individuals without and with cognitive impairment prefers to be informed about a diagnosis of dementia for reasons pertaining to autonomy.

Toward A Simple Diagnostic Index for Acute Uncomplicated Urinary Tract Infections

PURPOSE Whereas a diagnosis of acute uncomplicated urinary tract infection (UTI) in clinical practice comprises a battery of several diagnostic tests, these tests are often studied separately (in isolation from other test results). We wanted to determine the value of history and urine tests for diagnosis of uncomplicated UTIs, taking into account their mutual dependencies and information from preceding tests. METHODS Women with painful and/or frequent micturition answered questions about their signs and symptoms (history) of UTIs and underwent urine tests. A culture was the reference standard (103 colony-forming units per milliliter). A diagnostic index was derived using logistic regression with bootstrapped backward selection and parameter-wise shrinkage. Risk thresholds for UTI of 30% and 70% were used to analyze discriminative properties. Six models were compared: (1) history only, (2) history+ urine dipstick, (3) history+ urine dipstick + urinary sediment, (4) history+ urine dipstick+ dipslide, and (5) history+ urine dipstick+ urinary sediment+ dipslide; we then added (6) a test only for patients with an intermediate risk (between 30% and 70%) after the preceding test. RESULTS One hundred ninety-six women were included (UTI prevalence 61%). Seven variables were selected from history (3), dipstick (2), sediment (1), and dipslide (1). History correctly classified 56% of patients as having a UTI risk of either <30% or >70%. History and urine dipstick raised this to 73%. The 3 models with the addition of urinary sediment and dipslide, separately and in combination, performed hardly better. The sixth model, in which those at intermediate risk after history and received an additional test, correctly classified 83%. The patient’s suspicion of a UTI and a positive nitrite test were the strongest indicators of a UTI. CONCLUSIONS Most women with painful and/or frequent micturition can be correctly classified as having either a low or a high risk of UTI by asking 3 questions: Does the patient think she has a UTI? Is there at least considerable pain on micturition? Is there vaginal irritation? Other women require additional urine dipstick investigation. Sediment and dipslide have little added value. External validation of these recommendations is required before they are implemented in practice.