[Is dementia preventable through intensive vascular care? The preDIVA trial]. / Is dementie te voorkomen door intensieve vaatzorg?

OBJECTIVE: To assess whether intensive vascular care in GP practices can prevent dementia in a population of community-dwelling older people. METHOD: This pragmatic cluster-randomised open-label study (ISRCTN29711771) was conducted in persons aged 70-78 years who were registered with Dutch GP practices. The only exclusion criteria were a diagnosis of dementia and limited life expectancy. Practices were randomly assigned to an intervention arm or a control arm. Participants in the interventional arm underwent a cardiovascular check-up every 4 months for six years by a practice nurse. Primary outcomes were cumulative incidence of dementia and functional limitations. Main secondary outcomes were the incidence of cardiovascular disease and mortality. RESULTS: Between June 2006 and March 2009, 116 GP practices (3526 participants) were recruited and randomly assigned: 63 (1890 participants) 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. In this period, dementia was diagnosed in 121/1853 (6.5%) participants in the intervention group and in 112/1601 (7.0%) participants in the control group. This difference was not significant (hazard ratio 0.92, 95% CI 0.71-1.19). No differences were found with regard to functional decline, incident cardiovascular disease and mortality. CONCLUSION: Long-term intensive vascular care for community-dwelling elderly patients, provided in a primary care setting, does not result in a reduced incidence of dementia, functional limitations or mortality. There is, however, possibly an effect in elderly patients with untreated or sub-optimally treated hypertension; this warrants further research.

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.

Vascular risk factors and dementia--towards prevention strategies.

Several cohort studies have shown that vascular risk factors including hypertension, hypercholesterolaemia, diabetes mellitus, smoking, obesity and lack of physical exercise in midlife and to a lesser extent in late life, are associated with an increased risk of dementia. The results from randomised controlled clinical trials on treatment of these risk factors are not conclusive for the effect on cognitive decline and dementia. Studies investigating the effect of a multi-component intervention aimed at vascular risk factors to prevent or slow down cognitive decline and dementia will hopefully give the answer as to whether such an intervention is efficacious. This requires large clinical trials in an elderly population with long follow-up and several competing risks, making it difficult from an organisational and methodological point of view. Major challenges for future studies are to select the optimal population, set the optimal treatment targets and select clinically relevant outcome parameters.

Methodological issues in a cluster-randomized trial to prevent dementia by intensive vascular care.

OBJECTIVES: Description of methodological issues in a trial designed to evaluate if a multi-component intervention aimed at vascular risk factors can prevent dementia. DESIGN, SETTING AND PARTICIPANTS: Multi-center, open, cluster-randomized controlled clinical trial (preDIVA) including 3535 non-demented subjects aged 70-78, executed in primary practice and coordinated from one academic hospital. General practices are randomized to standard care or intensive vascular care. INTERVENTION: Vascular care consists of 4-monthly visits to a practice nurse who monitors all cardiovascular risk factors. Hypertension, hypercholesterolemia, overweight, lack of physical exercise and diabetes are strictly controlled according to a protocol and treated in a way, tailored to the characteristics of individual participants. MEASUREMENTS: Primary outcomes are incident dementia and disability; secondary outcomes are mortality, vascular events (stroke, myocardial infarction, peripheral vascular disease), cognitive decline and depression. RESULTS: Between May 2006 and February 2009, 3535 subjects from 115 general practices have been included. The clusters have an average size of 31 (SD 22, range 2-114). 1658 Patients from 52 practices were randomized to the standard care condition and 1877 patients in 63 practices to the vascular care condition. DISCUSSION: When designing a cluster-randomized trial, clustering of patient data within GP practices leads to a loss of power. This should be adjusted for in the power calculation. Since intensive vascular care will probably lead to a reduction in cardiovascular mortality, the competing risks of mortality and dementia should be taken into account.