Suzanne A. Ligthart

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.

Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer's disease in non-depressed subjects

Background: Apathy is a common symptom in various neuropsychiatric diseases including mild cognitive impairment (MCI) and dementia. Apathy may be associated with an increased risk of cognitive decline. The objective of this study was to investigate if apathy predicts the progression from MCI to Alzheimer’s disease (AD). Methods: The Alzheimer’s Disease Neuroimaging Initiative is a prospective multicentre cohort study. At baseline, 397 patients with MCI without major depression were included. Clinical data and the Geriatric Depression Scale at baseline were used. Apathy was defined based on the 3 apathy items of the 15-item Geriatric Depression Scale. The main outcome measure was the association of apathy with progression from MCI to AD. Results: During an average follow-up of 2.7 years (SD 1.0), 166 (41.8%) patients progressed to AD. The presence of symptoms of apathy without symptoms of depressive affect increased the risk of progression from MCI to AD (hazard ratio = 1.85, 95% CI = 1.09–3.15). Apathy in the context of symptoms of depressive affect or symptoms of depressive affect alone, without apathy, did not increase the risk of progression to AD. Conclusions: Symptoms of apathy, but not symptoms of depressive affect, increase the risk of progression from MCI to AD. Apathy in the context of symptoms of depressive affect does not increase this risk. Symptoms of apathy and depression have differential effects on cognitive decline.

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.

Cardiovascular risk management in community-dwelling elderly: opportunities for prevention.

Background: There is little information on the prevalence of hypertension and other modifiable cardiovascular risk factors in community-dwelling elderly in the Netherlands and the potential impact of improving antihypertensive treatment on major cardiovascular events. Design: Cross-sectional analysis of Dutch community-dwelling subjects aged 70–78 years without dementia who were included in the cluster randomized preDIVA trial (Prevention of Dementia by Intensive Vascular care). Methods: The prevalence of hypertension and other cardiovascular risk factors are described for participants with and without a history of cardiovascular disease (CVD). Projected benefits of blood pressure decrease are calculated using data from a meta-analysis and a large national registry. Results: Of 3534 subjects, more than one-third (n = 1230, 35.2%) have a history of cardiovascular disease. Overall, 63% of subjects have two or more cardiovascular risk factors amenable to treatment. Systolic blood pressure (SBP) is ≥160 mmHg in 37% of patients with CVD, of which 28% is untreated. In subjects without a history of CVD, 41% have a SBP ≥ 160 mmHg of which 52% is untreated. A 5–15 mmHg decrease in SBP is projected to prevent 12–32% of coronary heart disease and 16–41% of strokes, respectively. This corresponds with 14–38 prevented cases within 2 years in our intervention group (n = 1895). Conclusions: Hypertension and other cardiovascular risk factors are very common in elderly subjects. Current (primary and secondary) prevention programmes appear insufficient. Improved antihypertensive treatment has the potential to prevent a substantial proportion of strokes and coronary heart disease in this population.

Apathy is an independent risk factor for incident cardiovascular disease in the older individual: a population-based cohort study.

Although depression is considered to be associated with cardiovascular disease (CVD), specifically symptoms of apathy have been strongly associated with a history of CVD in recent studies. In this study, we prospectively assess whether symptoms of apathy and depression are independent risk factors for incident CVD and stroke.

Perspectives of older people engaging in nurse-led cardiovascular prevention programmes: a qualitative study in primary care in the Netherlands

Background Cardiovascular prevention programmes are increasingly being offered to older people. To achieve the proposed benefits, adherence is crucial. Understanding the reasons for adherence and non-adherence can improve preventive care. Aim To gain insight into what motivates older people living in the community to partake in a cardiovascular prevention programme, and reasons for subsequent continuation or withdrawal. Design and setting Qualitative study of current and former participants of the ongoing ≥6 year PreDIVA (prevention of dementia by intensive vascular care) trial in primary care practices in suburban areas in the Netherlands. Method Semi-structured interviews were conducted with a purposive sample of 15 participants (aged 76–82 years). Interviews were audiorecorded and analysed by two independent researchers using a thematic approach. Participants were asked about their motivation for participating in the programme, along with the facilitators and barriers to continue doing so. Results Responders reported that regular check-ups offered a feeling of safety, control, or being looked after, and were an important motivator for participation. For successful continuation, a personal relationship with the nurse and a coaching approach were both essential; the lack of these, along with frequent changes of nursing staff, were considered to be barriers. Participants considered general preventive advice unnecessary or patronising, but practical support was appreciated. Conclusion To successfully engage older people in long-term, preventive consultations, the approach of the healthcare provider is crucial. Key elements are to offer regular check-ups, use a coaching approach and to build a personal relationship with the patient.

The mediating role of cardiovascular risk factors in the relationship between symptoms of apathy and incident cardiovascular disease in community-dwelling older individuals

BACKGROUND In old age, both apathy and depression have been associated with an increased cardiovascular disease (CVD) risk. This study evaluated the mediating role of cardiovascular risk factors in the relationship of apathy and mood symptoms with incident CVD. METHODS Prospective cohort study of 1,790 community-dwelling older individuals (70-78 years) without a history of CVD or stroke. At baseline, apathy and mood symptoms were assessed with the 15-item Geriatric Depression Scale (GDS-15), of which three items represent apathy symptoms. The mediational risk factors included were diabetes mellitus (DM), body mass index (BMI), current smoking, physical inactivity, systolic blood pressure, and total cholesterol. Incident CVD was evaluated after two years of follow-up. Data were analyzed using structural equation modeling (SEM). RESULTS Incident CVD occurred in 59 (3.3%) participants. Apathy symptoms had a significant estimated total effect on incident CVD, with increases of 2.2% for each unit increase in apathy score. Of this total effect, 22.7% was due to the mediational effects of physical inactivity (13.6%), current smoking (4.5%), and DM (4.5%). The remaining 77.3% was due to direct effects reflecting other mediational dynamics. No significant (in)direct effects of mood symptoms on incident CVD were found. CONCLUSIONS Physical inactivity, smoking, and DM account for nearly one-fourth of the variation reflecting the link between apathy symptoms and incident CVD. This illustrates the relevance of unfavorable health behaviors and assessment of DM in older individuals with apathy. The majority of the effect of apathy symptoms on incident CVD is caused by other, yet unknown, factors.

Improving Prediction of Dementia in Primary Care

PURPOSE The Mini-Mental State Examination (MMSE) is one of the most widely used instruments to screen for cognitive deficits; however, this instrument alone is not sensitive enough to detect early symptoms of dementia. We aimed to investigate whether additionally using the Visual Association Test (VAT) improves the predictive value of the MMSE score for development of dementia. METHODS Analyses were based on data from 2,690 primary care patients aged 70 to 78 years who participated in the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial. We assessed change in the 30-point MMSE score over 2 years and the VAT score at 2 years—dichotomized as perfect (6 points) or imperfect (≤5 points)—and evaluated the predictive values of these tests for a diagnosis of dementia in the subsequent 4 to 6 years. Data were analyzed with logistic regression analysis. RESULTS Patients having a decline of 2 points or more in total MMSE score over 2 years had an odds ratio of 3.55 (95% CI, 2.51–5.00) for developing dementia. Patients having the same decline in MMSE score plus an imperfect VAT score had an odds ratio of 9.55 (95% CI, 5.89–15.41) for developing dementia. A 1-point decline in MMSE score increased odds of dementia only when the VAT score was imperfect. Dementia risk for patients with a 2- or 3-point decrease in MMSE score and a perfect VAT score did not differ significantly from the average risk of the cohort as a whole. CONCLUSIONS Administering the VAT in patients with a small decline on the MMSE over a 2-year period has substantial incremental value for identifying those at elevated risk for developing dementia. This simple test may help distinguish older adults who need further cognitive examination from those in whom a watchful waiting policy is justified.

PREVENTION OF DEMENTIA BY INTENSIVE VASCULAR CARE (PREDIVA): A CLUSTER-RANDOMIZED TRIAL

O4-05-01 PREVENTION OF DEMENTIA BY INTENSIVE VASCULAR CARE (PREDIVA): A CLUSTERRANDOMIZED TRIAL Edo Richard, Eric P. Moll van Charante, Lisa S. Eurelings, JanWillem van Dalen, Suzanne A. Ligthart, Emma F. van Bussel, Marieke P. Hoevenaar, Marinus Vermeulen, Willem A. van Gool, 1 Academic Medical Center, Amsterdam, Netherlands; 2 Radboud University Medical Center, Nijmegen, Netherlands. Contact e-mail: e.richard@amc. uva.nl

Improving cardiovascular risk management in elderly to prevent dementia: The preDIVA trial in progress

working memory, speed of processing, and spatial problem solving. To assess the neurobiological effects of cognitive training, event-related potentials (ERPs) were measured in a subset of participants during performance of a source memory task. Follow-up testing will be conducted immediately post cognitive training and at six monthly intervals for a 2 year follow-up period. A control group (N1⁄4 300, Age1⁄4 61.90, SD1⁄4 7.16 yrs) completed the computerized test battery at 3-monthly intervals for 1 year. Results: Results from the follow-up testing conducted immediately post cognitive training indicate that, compared to controls, ACE participants showed significantly improved performance on cognitive function tests measuring visual learning and memory, attention/working memory, and executive function. Small, but non-significant, improvements in measures of processing speed were also observed. ACE participants also reported significant improvement in everyday memory functioning and increased physical exercise. Results from the 6 and 12-month follow-up testing will be available at the time of the conference. Conclusions: Preliminary results indicate that providing older adults with cognitive training produced immediate post-training improvements on tests of cognitive function and subjective measures of everyday memory. Of particular importance will be to determine whether these immediate improvements in cognitive function are maintained in the longer-term follow-up testing.