Summary Interventions that have even quite modest effects at the individual level could drastically reduce the future burden of dementia associated with Alzheimer's disease at the population level. ...In the past three decades, both pharmacological and lifestyle interventions have been studied for the prevention of cognitive decline or dementia in randomised controlled trials of individuals mostly aged older than 50–55 years with or without risk factors for Alzheimer's disease. Several trials testing the effects of physical activity, cognitive training, or antihypertensive interventions showed some evidence of efficacy on a primary cognitive endpoint. However, most of these trials had short follow-up periods, and further evidence is needed to confirm effectiveness and establish the optimum design or dose of interventions and ideal target populations. Important innovations in ongoing trials include the development of multidomain interventions, and the use of biomarker or genetic inclusion criteria. Challenges include the use of adaptive trial designs, the development of standardised, sensitive outcome measures, and the need for interventions that can be implemented in resource-poor settings.
Summary Background Prevention strategies are urgently needed to tackle the growing burden of Alzheimer's disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract ...for the reduction of incidence of Alzheimer's disease in elderly adults with memory complaints. Methods In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer's disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov , number NCT00276510. Findings Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer's disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio HR 0·84, 95% CI 0·60–1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69–1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77–1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups. Interpretation Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer's disease compared with placebo. Funding Ipsen.
Summary Background No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the ...prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. Methods The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov ( NCT00672685 ). Findings 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (−0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (−0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. Interpretation The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. Funding French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.
Nutrition and Cognition in Aging Adults Coley, Nicola; Vaurs, Charlotte; Andrieu, Sandrine
Clinics in geriatric medicine,
08/2015, Volume:
31, Issue:
3
Journal Article
Peer reviewed
Numerous longitudinal observational studies have suggested that nutrients, such as antioxidants, B vitamins, and ω-3 fatty acids, may prevent cognitive decline or dementia. There is very little ...evidence from well-sized randomized controlled trials that nutritional interventions can benefit cognition in later life. Nutritional interventions may be more effective in individuals with poorer nutritional status or as part of multidomain interventions simultaneously targeting multiple lifestyle factors. Further evidence, notably from randomized controlled trials, is required to prove or refute these hypotheses.
We aimed to describe longitudinal patterns of care in community-dwelling European patients with Alzheimer disease (AD), and determine patient-, caregiver-, and country-related predictors of ...transitions across different care levels.
Two-year follow-up data from ICTUS cohort (1375 patients with AD, 12 countries) were analyzed using multistate Markov models to describe transitions across states of care and identify their predictors.
Of the patients, 61.3% stayed in the same state during follow-up, and only 9.5% experienced ≥2 changes between states. Six-month transition probabilities were 11% for informal to formal care and 13% for formal to informal care (in the community). Older age, male gender, poorer cognitive and behavioral scores, and country of residence were associated with transitioning from informal to formal care, but only country of residence was associated with the reverse transition.
Changes between different types of care were rare during follow-up, and country factors in particular influenced these transitions.
To describe hospitalizations in a Special Acute Care inpatient Unit for older adults with Alzheimer's disease (AD) and other related disorders.
An 11-year observational study of consecutive ...hospitalizations from 1996 to 2006.
The Alzheimer Special Acute Care inpatient Unit in the Geriatrics Department of the Toulouse University Hospital, France.
A total of 4708 patients with dementia accounting for 6299 consecutive hospitalizations.
Data regarding admission causes, cognition, physical disability, nutritional assessment, behavioral and psychological symptoms of dementia, and sociodemographics were recorded.
Data from 6299 hospitalizations are presented: 4708 (74.7%) hospitalizations accounted for first-time admissions and 1591 (25.3%) were rehospitalizations. Among the first-time admissions, complications of dementia and cognitive diagnosis experienced a significant switch in frequency. Whereas until 2001, the main cause of admission was for a diagnosis (51%), complications became the primary cause from 2003 onward with a significant increasing trend (56%) (P < .001). The most frequent cause of complications was behavioral and psychological symptoms of dementia, with a significant trend for an increased frequency (P < .001). Agitation-aggressiveness represented 60% of behavioral and psychological symptoms of dementia. Between 1996 and 2006, the age of patients at first-time admission gradually increased over time, as did the severity of cognitive impairment and the prevalence of unsatisfactory nutritional status (P for trend < .001 for each variable).
The evolving patient characteristics and the causes of first-time admissions changed over the course of 11 years. Behavioral and psychological symptoms of dementia, especially agitation-aggressiveness, have progressively become the key drivers of Special Acute Care inpatient Unit hospitalizations. These findings suggest that the role, mission, and functioning of the Special Acute Care inpatient Unit within the Alzheimer care system has been modified over time.
Summary Harmful consequences in health status caused by disease are referred to as outcomes, and in clinical studies the measures of these outcomes are called endpoints. A major challenge when ...deciding on endpoints is to represent the outcomes of interest accurately, and the accuracy of such representation is assessed through validation. Complex diseases like Alzheimer's disease have many different and interdependent outcomes. We present a consensus for endpoints to be used in clinical trials in Alzheimer's disease, agreed by a European task force under the auspices of the European Alzheimer Disease Consortium. We suggest suitable endpoints for primary and secondary prevention trials, for symptomatic and disease-modifying trials in very early, mild, and moderate Alzheimer's disease, and for trials in severe Alzheimer's disease. A clear and consensual definition of endpoints is crucial for the success of further clinical trials in the field and will allow comparison of data across studies.
Although web-based interventions have been promoted for cardiovascular risk management over the past decade, there is limited evidence for effectiveness of these interventions in people older than 65 ...years. The healthy ageing through internet counselling in the elderly (HATICE) trial aimed to determine whether a coach-supported internet intervention for self-management can reduce cardiovascular risk in community-dwelling older people.
This prospective open-label, blinded endpoint clinical trial among people age 65 years or over at increased risk of cardiovascular disease randomly assigned participants in the Netherlands, Finland, and France to an interactive internet intervention stimulating coach-supported self-management or a control platform. Primary outcome was the difference from baseline to 18 months on a standardised composite score (Z score) of systolic blood pressure, LDL cholesterol, and body-mass index (BMI). Secondary outcomes included individual risk factors and cardiovascular endpoints. This trial is registered with the ISRCTN registry, 48151589, and is closed to accrual.
Among 2724 participants, complete primary outcome data were available for 2398 (88%). After 18 months, the primary outcome improved in the intervention group versus the control group (0·09 vs 0·04, respectively; mean difference −0·05, 95% CI −0·08 to −0·01; p=0·008). For individual components of the primary outcome, mean differences (intervention vs control) were systolic blood pressure −1·79 mm Hg versus −0·67 mm Hg (−1·12, −2·51 to 0·27); BMI −0·23 kg/m2 versus −0·08 kg/m2 (−0·15, −0·28 to −0·01); and LDL −0·12 mmol/L versus −0·07 mmol/L (−0·05, −0·11 to 0·01). Cardiovascular disease occurred in 30 (2·2%) of 1382 patients in the intervention versus 32 (2·4%) of 1333 patients in the control group (hazard ratio 0·86, 95% CI 0·52 to 1·43).
Coach-supported self-management of cardiovascular risk factors using an interactive internet intervention is feasible in an older population, and leads to a modest improvement of cardiovascular risk profile. When implemented on a large scale this could potentially reduce the burden of cardiovascular disease.
European Commission Seventh Framework Programme.
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