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Objectives: Elevated total plasma homocysteine is a risk factor for Alzheimer's disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical β-amyloid (Aβ) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored. Design: This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial. Setting: French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia. Participants: Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical Aβ load. Measurements: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models. Results: We found that total baseline plasma homocysteine was not significantly associated with cortical Aβ as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E ε4 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical Aβ in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E ε4 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66). Conclusions: The role of n-3 PUFAs on the relationship between homocysteine and cerebral Aβ warrants further investigation. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the changes in specific domains of cognitive function in older adults reporting subjective memory complaints with a low omega-3 index receiving omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or placebo. Design: This is a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT) using subjects randomized to the n-3 PUFA supplementation or placebo group. Setting: French community dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia. Participants: A subgroup of MAPT subjects in the lowest quartile of omega-3 index distribution with baseline values ≤ 4.83 % (n = 183). Intervention: The n-3 PUFA supplementation group consumed a daily dose of DHA (800 mg) and EPA (a maximum amount of 225 mg) for 3 years. The placebo group received identical capsules comprising liquid paraffin oil. Measurements: Linear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in eight cognitive tests over 36 months. Results: There was less decline on the Controlled Oral Word Association Test (COWAT) in the n-3 PUFA supplementation group compared to placebo (p = 0.009; between group mean difference over 36 months, 2.3; 95% CI, 0.6,4.0). No significant differences for any of the other cognitive tests were found, including other tests of executive functioning, although, numerically all results were in favour of the n-3 PUFA supplementation. Conclusions: We found some evidence that n-3 PUFAs might be beneficial for the maintenance of executive functioning in older adults at risk of dementia with low omega-3 index, but this exploratory finding requires further confirmation. A larger specifically designed randomised controlled trial could be merited. [ABSTRACT FROM AUTHOR]

interventions are crucial as they offer simple and inexpensive public health solutions that will be useful over the long term use. A Task Force on designing trials of nutritional interventions to slow cognitive decline in older adults was held in Toulouse in September 2012. The aim of the Task Force was to bring together leading experts from academia, the food industry and regulatory agencies to determine the best trial designs that would enable us to reach our goal of maintaining or improving cognitive function in apparently healthy aging people. An associated challenge for this Task Force was to determine the type of trials required by the Public Food Agencies for assessing the impact of nutritional compounds in comparison to well established requirements for drug trials. Although the required quality of the study design, rationale and statistical analysis remains the same, the studies designed to show reduction of cognitive decline require a long duration and the objectives of this task force was to determine best design for these trials. Two specific needs were identified to support trials of nutritional interventions: 1- Risk-reduction strategies are needed to tackle the growing burden of cognitive decline that may lead to dementia, 2- Innovative study designs are needed to improve the quality of these studies. [ABSTRACT FROM AUTHOR]

Background: The efficacy of cholinesterase inhibitors (ChEIs), especially over the long term, is still under discussion. There is a lack of data concerning the optimal drug treatment duration and the reasons for discontinuation, particularly outside the clinical trial setting.Objective: To identify predictive factors of discontinuation and switch of ChEIs in a real-world setting.Methods: A multicentre cohort study of 686 patients with mild-to-moderate ambulatory Alzheimer's disease who were diagnosed in 16 Alzheimer's disease expert centres in 2000-2 and who were assessed twice yearly for 2 years. The main outcome measure was ChEI discontinuation and switch (analysed using Cox survival analyses).Results: After 2 years, of the 611 subjects treated with a ChEI at baseline, 100 subjects had switched or discontinued ChEI therapy (incidence rate 12.7 [95% CI 10.2, 15.2] per 100 person-years). The incidences of switching and discontinuation were 9.2 (95% CI 7.0, 11.3) and 3.6 (95% CI 2.3, 4.8) per 100 person-years, respectively. In the multivariate analysis, predictive factors for switching were an ineffective ChEI dose (adjusted hazard ratio [HR(a)] = 6.91, 95% CI 3.08, 15.49), rapid cognitive decline (HR(a) = 4.10, 95% CI 1.85, 9.05), hospitalization unrelated to Alzheimer's disease (HR(a) = 2.33, 95% CI 1.07, 5.09) and anxiety (HR(a) = 2.08, 95% CI 1.16, 3.73). Predictive factors of discontinuation were: hospitalization related (HR(a) = 9.14, 95% CI 2.69, 31.07) or unrelated (HR(a) = 4.23, 95% CI 1.54, 11.59) to Alzheimer's disease, use of an anticholinergic drug (HR(a) = 4.26, 95% CI 1.46, 12.45) and weight loss (HR(a) = 3.77, 95% CI 1.15, 12.33).Conclusions: This study highlights four types of predictors of switch or discontinuation, reflecting disease progression, reconsideration of ChEI benefits, adverse drug reactions to ChEIs and inappropriate concurrent use of anticholinergic drugs. Attention should be paid to anticholinergic agents and prescribers should be given better information about these drugs. [ABSTRACT FROM AUTHOR]

Memory complaints are relatively common in elderly people, although they are not always reported to the general practitioner (GP). These subjective complaints do not necessarily correlate with objective measures of memory impairment or cognitive performance, but they may be an early indication of impairment at a state that is undetectable by standard testing instruments. Memory complaints may also predict future cognitive decline. The GuidAge study is a secondary prevention trial for Alzheimer's disease involving non-demented individuals aged 70 years or older having spontaneously complained of memory problems to their GP. More than half of participants had a Clinical Dementia Rating score of 0.5 at baseline. The percentage of participants reporting problems on the McNair and Kahn scale varied from 6.2% to 78.6% per item. Certain specific memory complaints may be more related than others to the beginning of the neurodegenerative process, and could predict future cognitive decline. The importance of memory complaints should not be underestimated in clinical practice. [ABSTRACT FROM AUTHOR]

Attrition, defined as a total loss to follow-up of participants, is a potential major bias in clinical trials. Participants can be lost for many reasons (death, illness, worsened health, refusal, withdrawal, lost to follow up). Attrition may be higher in older populations, so geriatric researchers should pay particular attention to the difficulties it raises. For a proper interpretation of research findings, a detailed analysis of the type of attrition observed and its possible determinants is essential, to determine if attrition has occurred at random or if it is associated to certain patient or treatment characteristics. This paper aims to review different causes of attrition, its prevalence among studies in different elderly populations, and its consequences on research findings. In addition, strategies used to minimise attrition (tracking, bonding, incentives) are discussed, and methods proposed to take this phenomenon into account are proposed. [ABSTRACT FROM AUTHOR]

Background: In the domain of Alzheimer's disease (AD) prevention, various potentially protective factors have been identified in epidemiological studies. Although the results of these observational studies have been relatively consistent, the results of intervention studies remain disappointing. Methodological problems could explain these negative results, like the selection of the population; a plausible assumption is that the older people who agree to take part in these intervention studies differ from those who refuse, and are those that are least likely to benefit from such programs. The aim of this study was (i) to study the determinants of participation in and adhesion to a prevention trial in a population of older individuals via a quantitative approach using a questionnaire, (ii) to study the representations and practices of prevention in this population using a qualitative approach using semi-structured interviews and focus groups. Method: The study population for the ACCEPT study was recruited at the time of inclusion of subjects in a prevention trial. The population was made up of persons aged 70 years or older, living at home and demonstrating some form of frailty, defined as a spontaneous memory complaint to their general practitioner or difficulties in carrying out instrumental activities of daily living. We used a quantitative approach based on the administration of a self-completed questionnaire sent to 1680 subjects having accepted to take part in the prevention trial, and to the sample of subjects meeting the inclusion criteria but having refused to take part. The qualitative approach, carried out at the moment of inclusion, involved subjects that having accepted to take part and subjects that having refused. Semi-structured interviews were carried out in order to understand the logic leading to refusal or acceptance. Conclusion: The analysis of the results will combine the viewpoints of the different disciplines. It will allow us to better understand the logic at work, to characterise the populations at risk of refusal, and perhaps to remove some of the barriers to participation in prevention programs. The identification of such barriers will provide feedback in terms of the conception and management of prevention measures. [ABSTRACT FROM AUTHOR]