Tuesday, February 23, 2016
Monday, November 03, 2014
Thursday, June 12, 2014
Tuesday, December 25, 2012
PLYMOUTH, United Kingdom -- December 19, 2012 -- New research suggests that the cognitive test used in Alzheimer's disease (AD) drug trials is flawed.
The current standard cognitive test for the disease is the ADAS Cog. The new research, published as 2 studies in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association, investigates the role of the test and questions its effectiveness.
The studies show that the ADAS Cog is not subtle enough to properly track changes in the early stages of AD. This is important because data from this key stage is required to show whether or not a new drug is working.
Researchers also showed that the modern method of "Rasch analysis" confirmed the flaw.
In the first study, researchers examined 675 measurements from people aged 53 to 90 years with mild Alzheimer's disease across 5 time points -- 0, 6, 12, 18 and 24 months.
In terms of final patient score the ADAS-cog seemed sound. But by breaking down all the data to component level, a different story emerged: a "ceiling effect" was exposed for 8 out of the 11 parts of the ADAS-cog with many patients, ranging from 32% to 83%, passing the section when in reality much greater variance between the patients almost certainly existed and needed scoring.
In the second study, the research team moved on to use the modern method of Rasch analysis to further test the data. This confirmed the flaw. The more sophisticated method of analysis also suggested a number of possible pathways to improvement including making parts of the ADAS-cog test more difficult as well as re-thinking the scoring structure.
As a consequence, the Plymouth-based research team is suggesting urgent changes to the ADAS Cog and is not ruling out the need for a new test.
"It is impossible to say precisely the extent to which the ADAS Cog's flaws have undermined the numerous clinical trials in which it has been used," said Jeremy Hobart, MD, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, United Kingdom. "It has been used, unchanged, for many years and its apparent contribution to suboptimal trials has led a number of drug companies to rethink their strategies."
"However, it is very clear that in its current form the ADAS Cog underestimates cognitive differences between people and changes over time," he said. "To determine if treatments, developed from painstaking years of research, work in expensive studies we need to invest in developing measurement instruments that are fit for purpose. This requires the routine use of different methods. In its current form, the ADAS Cog is not working in people with mild Alzheimer's disease."
Saturday, September 29, 2012
Raloxifene improves verbal memory in late postmenopausal women: a randomized, double-blind, placebo-controlled trial; Jacobsen DE, Samson MM, Emmelot-Vonk MH, Verhaar HJ; Menopause (Nov 2009)
OBJECTIVE:: The aim of this study was to examine the effects of raloxifene compared with those of placebo on verbal memory, mental processing speed, depression, anxiety, and quality of life. METHODS:: A randomized, double-blind, placebo-controlled trial of 213 healthy women 70 years or older was conducted between July 2003 and January 2008 at the University Medical Centre Utrecht, the Netherlands. Participants were randomly assigned to receive raloxifene (60 mg) or placebo daily for 12 months. Measurements were taken at baseline and after 3, 6, and 12 months. The change in scores from baseline was calculated. The main outcome measures were direct and delayed verbal memory (Groningen 15 Words test), mental processing speed (Trails B test), mood/depression (Geriatric Depression Scale), anxiety (State-Trait Anxiety Inventory 1 and 2), and quality of life (Women's Health Questionnaire and EuroQol-5 dimensional questionnaire). RESULTS:: Direct verbal memory improved significantly with raloxifene compared with placebo: the women receiving raloxifene repeated more words in the words A + B test than did the women receiving placebo (P = 0.025). At 12 months, the change from baseline was 16 words in the raloxifene group and 10 words in the placebo group. In the words A test, direct repetition was also significantly better among women receiving raloxifene than among women receiving placebo (P = 0.023), with the change from baseline in the number of words repeated being nine words in the raloxifene group and six words in the placebo group at 12 months. CONCLUSIONS:: In postmenopausal women, raloxifene gave significantly improved verbal memory when compared with placebo.
Increased risk of cognitive and functional decline in patients with atrial fibrillation: results of the ONTARGET and TRANSCEND studies; Marzona I, O'Donnell M, Teo K, Gao P, Anderson C, Bosch J, Yusuf S; Canadian Medical Association Journal (CMAJ) (Feb 2012)
BACKGROUND:The role of atrial fibrillation in cognitive impairment and dementia, independent of stroke, is uncertain. We sought to determine the association of atrial fibrillation with cognitive and physical impairment in a large group of patients at high cardiovascular risk. METHODS:We conducted a post-hoc analysis of two randomized controlled trials involving 31 546 patients, the aims of which were to evaluate the efficacy of treatment with ramipril plus telmisartan (ONTARGET) or telmisartan alone (TRANSCEND) in reducing cardiovascular disease. We evaluated the cognitive function of participants at baseline and after two and five years using the Mini-Mental State Examination (MMSE). In addition, we recorded incident dementia, loss of independence in activities of daily living and admission to long-term care facilities. We used a Cox regression model adjusting for main confounders to determine the association between atrial fibrillation and our primary outcomes: a decrease of three or more points in MMSE score, incident dementia, loss of independence in performing activities of daily living and admission to long-term care. RESULTS:We enrolled 31 506 participants for whom complete information on atrial fibrillation was available, 70.4% of whom were men. The mean age of participants was 66.5 years, and the mean baseline MMSE score was 27.7 (standard deviation 2.9) points. At baseline, 1016 participants (3.3%) had atrial fibrillation, with the condition developing in an additional 2052 participants (6.5%) during a median follow-up of 56 months. Atrial fibrillation was associated with an increased risk of cognitive decline (hazard ratio [HR] 1.14, 95% confidence interval [CI]1.03-1.26), new dementia (HR 1.30, 95% CI 1.14-1.49), loss of independence in performing activities of daily living (HR 1.35, 95% CI 1.19-1.54) and admission to long-term care facilities (HR 1.53, 95% CI 1.31-1.79). Results were consistent among participants with and without stroke or receiving antihypertensive drugs. INTERPRETATION:Cognitive and functional decline are important consequences of atrial fibrillation, even in the absence of overt stroke.
Can Mirtazapine Counteract the Weight Loss Associated With Alzheimer Disease? A Retrospective Open-label Study; Segers K, Surquin M; Alzheimer Disease & Associated Disorders (Jul 2012)
Sunday, August 26, 2012
Randomized, Double-Blind, Parallel-Group, 48-Week Study for Efficacy and Safety of a Higher-Dose Rivastigmine Patch (15 vs. 10 cm) in Alzheimer's Disease; Cummings J, Froelich L, Black SE, Bakchine S, Bellelli G, Molinuevo JL, Kressig RW, Downs P, Caputo A, Strohmaier C; Dementia and Geriatric Cognitive Disorders 33 (5), 341-353 (Jul 2012)
Wednesday, January 18, 2012
CSF profiles of tau and abeta are extremely effective differentiating some dementias but not others. Markers were t(total) tau, p (phosphorylated) tau, and Abeta42 in CSF. " AD profile" of markers was seen in AD, but also in many autopsy proven cases of DLB, CBD, FTLD and VaD (about 30-50 % of respective types of dementia patients had :AD profile." Psychiatric patients and those with subjective complaints of memory loss had normal CSF results. PSP patients had normal results also. CJD patients had very high t tau and normal p tau