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 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 In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging–Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's ...disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.
To evaluate the relationship of white matter hyperintensities (WMH) with decline in lower extremity function (LEF) over approximately 3 years in dementia-free older adults with memory complaints.
We ...obtained brain MRI data from 458 community-dwelling adults, aged 70 years or over, at baseline, and from 358 adults over an average follow-up of 963 days. We evaluated LEF using the Short Physical Performance Battery (SPPB). We related baseline WMH volumes and progression to SPPB scores over time, using mixed-effect linear regressions. For the secondary analyses, we categorized baseline WMH volume into quartiles, and dichotomized the WMH progression to compare fast and slow progression.
Baseline WMH volume (β = -0.017, 95% confidence interval CI -0.025 to -0.009), as well as WMH progression (β = -0.002, 95% CI -0.003 to -0.001), significantly associated with a decline in SPPB performance in adjusted analyses. Compared with the lowest quartile of baseline WMH volume, the highest quartile associated with a decline in SPPB performance (β = -0.301, 95% CI -0.558 to -0.044). Fast progression also associated with a decline in SPPB performance. We found clinically meaningful differences in the SPPB, with higher scores in participants with slow progression of WMH, at both 24 and 36 months.
Baseline level and WMH progression associated with longitudinal decline in SPPB performance among older adults. We detected clinically meaningful differences in SPPB performance on comparing fast with slow progression of WMH, suggesting that speed of WMH progression is an important determinant of LEF during aging.
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