Saturday, September 29, 2012

raloxifene and cognition

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.

AFIB and cognitive decline without stroke

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.

mitazepine for weight loss in AD

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)

Weight loss is a frequent complication of Alzheimer disease (AD), associated with increased morbidity and mortality. Increased appetite and weight gain are known side effects of the antidepressant mirtazapine. This analysis was undertaken to assess the safety and potential utility of mirtazapine to counteract weight loss in patients with AD or mixed AD (AD with cerebrovascular lesions). We performed a retrospective analysis of the clinical records of all outpatients attending our memory clinic for AD or mixed AD, who had received mirtazapine (30 mg daily) with the specific purpose of inducing weight or appetite gain. Data were available for a total of 22 patients (mean age, 80.9 y, 86.4% female). The mean weight at baseline was 52.4 kg and the mean BMI was 20.5 kg/m. 77.3% of the patients had gained weight after 3 months (mean gain, 1.93 kg or 3.9% of initial body weight) and 82.3% after 6 months (2.11 kg or 4.6%). One patient had to discontinue mirtazapine because of daytime sleepiness. Mirtazapine seems to be a safe and useful approach to counteract weight loss in AD, if possible in combination with nonpharmacological interventions. Body weight should be monitored during treatment to avoid excessive weight gain.

donepezil for LBD

Donepezil for dementia with Lewy bodies: A randomized, placebo-controlled trial; Mori E, Ikeda M, Kosaka K, on behalf of the Donepezil-DLB Study Investigators; Annals of Neurology 72 (1), 41-52 (Jul 2012)
OBJECTIVE: Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double-blind, placebo-controlled exploratory phase 2 trial. METHODS: One-hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini-Mental State Examination (MMSE) and several domain-specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III. RESULTS: Donepezil at 5 and 10mg/day was significantly superior to placebo on both the MMSE (5mg: mean difference, 3.8; 95% confidence interval [CI], 2.3-5.3; p<0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9-3.9; p = 0.001) and CIBIC-plus (p<0.001 for each); 3mg/day was significantly superior to placebo on CIBIC-plus (p<0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p<0.001) at 5 and 10mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups. INTERPRETATION: Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated. ANN NEUROL 2012;72:41-52.
Comment-- donepezil-- which is available as a once daily generic, is effective in LBD, therefore the more expensive rivastigmine patch is not needed.

Higher vitamin D level protective against AD?

Higher Vitamin D Dietary Intake Is Associated With Lower Risk of Alzheimer's Disease: A 7-Year Follow-up; Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Herrmann FR, Beauchet O; Journals of Gerontology: Series A, Biological Sciences and Medical Sciences (Apr 2012)
BACKGROUND: Hypovitaminosis D is associated with cognitive decline among older adults. The relationship between vitamin D intakes and cognitive decline is not well understood. Our objective was to determine whether the dietary intake of vitamin D was an independent predictor of the onset of dementia within 7 years among women aged 75 years and older. METHODS: Four hundred and ninety-eight community-dwelling women (mean, 79.8 ± 3.8 years) free of vitamin D supplements from the EPIDemiology of OSteoporosis Toulouse cohort study were divided into three groups according to the onset of dementia within 7 years (ie, no dementia, Alzheimer's disease [AD], or other dementias). Baseline vitamin D dietary intakes were estimated from self-administered food frequency questionnaire. Age, body mass index, initial cognitive performance, education level, physical activity, sun exposure, disability, number of chronic diseases, hypertension, depression, use of psychoactive drugs, and baseline season were considered as potential confounders. RESULTS: Women who developed AD (n = 70) had lower baseline vitamin D intakes (mean, 50.3 ± 19.3 μg/wk) than nondemented (n = 361; mean intake = 59.0 ± 29.9 μg/wk, p = .027) or those who developed other dementias (n = 67; mean intake = 63.6 ± 38.1 μg/wk, p = .010). There was no difference between other dementias and no dementia (p = .247). Baseline vitamin D dietary intakes were associated with the onset of AD (adjusted odds ratio = 0.99 [95% confidence interval = 0.98-0.99], p = .041) but not with other dementias (p = .071). Being in the highest quintile of vitamin D dietary intakes was associated with a lower risk of AD compared with the lower 4 quintiles combined (adjusted odds ratio = 0.23 [95% confidence interval = 0.08-0.67], p = .007). CONCLUSIONS: Higher vitamin D dietary intake was associated with a lower risk of developing AD among older women.
Comment see associated article about treating with memantine and vitamin D

Memantin plus vitamin D in Alzheimer's disease

Effectiveness of the combination of memantine plus vitamin d on cognition in patients with Alzheimer disease: a pre-post pilot study; Annweiler C, Herrmann FR, Fantino B, Brugg B, Beauchet O; Cognitive and Behavioral Neurology 25 (3), 121-7 (Sep 2012)
OBJECTIVE: To determine whether treatment with memantine plus vitamin D is more effective than memantine or vitamin D alone in improving cognition among patients with Alzheimer disease (AD). METHODS: We studied 43 white outpatients (mean 84.7±6.3 years; 65.1% women) with a new diagnosis of AD, who had not taken anti-dementia drugs or vitamin D supplements. We prescribed memantine alone (n=18), vitamin D alone (n=17), or memantine plus vitamin D (n=8) for an average of 6 months. We assessed cognitive change with the Mini-Mental State Examination (MMSE). We used age, sex, pre-treatment MMSE score, and duration of treatment as covariables. RESULTS: Before treatment, the 3 groups had comparable MMSE scores. At 6 months, participants taking memantine plus vitamin D increased their MMSE score by 4.0±3.7 points (P=0.034), while participants taking memantine alone remained stable (change of 0.0±1.8 points; P=0.891), as did those taking vitamin D alone (-0.6±3.1 points; P=0.504). Treatment with memantine plus vitamin D was associated with improvement in the MMSE score compared to memantine or vitamin D alone after adjustment for covariables (P<0.01). Mixed regression analysis showed that the visit by combined treatments (memantine plus vitamin D) interaction was significant (P=0.001), while memantine or vitamin D alone showed no effect. CONCLUSIONS: Patients with AD who took memantine plus vitamin D for 6 months had a statistically and clinically relevant gain in cognition, underlining possible synergistic and potentiating benefits of the combination.