Long term acetyl L carnitine treatment in Alzheimer's disease
A. Spagnoli, MD, U. Lucca, PhD, G. Menasce, MD, L. Bandera, MD, G. Cizza, MD, G. Forloni, PhD, M. Tettamanti, PhD, L. Frattura, MD, P. Tiraboschi, MD, M. Comelli, PhD, U. Senin, MD, A. Longo, MD, A. Petrini, MD, G. Brambilla, MD, A. Belloni, PhD, C. Negri, MD, F. Cavazzuti, MD, A. Salsi, MD, P. Calogero, MD, E. Parma, MD, M. Stramba-Badiale, MD, S. Vitali, MD, G. Andreoni, MD, M. R. Inzoli, MD, G. Santus, MD, R. Caregnato, MD, M. Peruzza, MD, M. Favaretto, MD, C. Bozeglav, PhD, M. Alberoni, MD, D. De Leo, MD, L. Serraiotto, MD, A. Baiocchi, MD, S. Scoccia, MD, P. Culotta, MD and D. Ieracitano, MD
ABSTRACT: In a double-blind, placebo-controlled, parallel-group, randomized clinical trial, we studied the efficacy of long-term (1-year) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer's disease. We employed 14 outcome measures to assess functional and cognitive impairment. After 1 year, both the treated and placebo groups worsened, but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, ideomotor and buccofacial apraxia, and selective attention. Adjusting for initial scores with analysis of covariance, the treated group showed better scores on all outcome measures, reaching statistical significance for the Blessed Dementia Scale, logical intelligence, verbal critical abilities, long-term verbal memory, and selective attention. The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample. Reported adverse events were relatively mild, and there was no significant difference between the treated and placebo groups either in incidence or severity.
Abstract: In a double-blind, placebo study, acetyl-L-carnitine was administered to 7 probable Alzheimer's disease patients who were then compared by clinical and 31P magnetic resonance spectroscopic measures to 5 placebo-treated probable AD patients and 21 age-matched healthy controls over the course of 1 year. Compared to AD patients on placebo, acetyl-L-carnitine-treated patients showed significantly less deterioration in their Mini-Mental Status and Alzheimer's Disease Assessment Scale test scores. Furthermore, the decrease in phosphomonoester levels observed in both the acetyl-L-carnitine and placebo AD groups at entry was normalized in the acetyl-L-carnitine-treated but not in the placebo-treated patients. Similar normalization of high-energy phosphate levels was observed in the acetyl-L-carnitine-treated but not in the placebo-treated patients. This is the first direct in vivo demonstration of a beneficial effect of a drug on both clinical and CNS neurochemical parameters in AD.
A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease
L. J. Thal, MD, A. Carta, MD, W. R. Clarke, PhD, S. H. Ferris, PhD, R. P. Friedland, MD, R. C. Petersen, MD, PhD, J. W. Pettegrew, MD, E. Pfeiffer, MD, M. A. Raskind, MD, M. Sano, PhD, M. H. Tuszynski, MD, PhD and R. F. Woolson, PhD
doi: 10.1212/WNL.47.3.705Neurology September 1996 vol. 47 no. 3 705-711
Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease
Montgomery, Stuart A.a; Thal, L.J.b; Amrein, R.c
Abstract: The efficacy of acetyl-L-carnitine (gamma-trimethyl-β-acetylbutyrobetaine (Alcar) in mild cognitive impairment (MCI) and mild (early) Alzheimer's disease (AD) was investigated with a meta-analysis of double-blind, placebo-controlled prospective, parallel group comparison studies of at least 3 months duration. The duration of the studies was 3, 6 or 12 months and the daily dose varied between studies from 1.5–3.0 g/day. An effect size was calculated to reflect the results of the variety of measures used in the studies grouped into the categories of clinical tests and psychometric tests. The effect sizes from the categories were integrated into an overall summary effect size. The effect size for the Clinical Global Impression of Change (CGI-CH) was calculated separately. Meta-analysis showed a significant advantage for Alcar compared to placebo for the integrated summary effect [ESall scales=0.201, 95% confidence interval (CI)=0.107–0.295] and CGI-CH (ESCGI-CH=0.32, 95% CI=0.18–0.47). The beneficial effects were seen on both the clinical scales and the psychometric tests. The advantage for Alcar was seen by the time of the first assessment at 3 months and increased over time. Alcar was well tolerated in all studies.
Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression.
a Chemical Works of Gedeon Richter Ltd., Budapest, Hungary
b National Stroke Centre, Hüvösvölgyi út 116, Budapest H-1021, Hungary
Available online 9 April 2002
Abstract: Objective: To investigate the effect of vinpocetine on cerebral blood flow (CBF) in the compromised circulation of a stroke affected hemisphere using transcranial Doppler (TCD) and near infrared spectroscopy (NIRS) methods. Methods: 43 patients with ischemic stroke were randomized into vinpocetine (VP) and placebo group in a double blind, placebo-controlled study of the effect of a single-dose i.v. infusion of vinpocetine on cerebral blood perfusion and oxygenation. In the VP group 20 mg VP in 500 ml saline, in the placebo group 500 ml saline alone were administered. The concentrations of oxy-, reduced- and total hemoglobin were measured by NIRS frontolaterally on the side of lesion while the mean cerebral blood flow velocity (CBFV), the pulsatility index (PI) and Doppler spectral intensity (DSI) were monitored by TCD in the middle cerebral artery on the same side. Values were averaged for the first 5 min prior to the infusion and for the last 5 min of infusion and they were compared between groups. Results:The concentration of all three chromophores increased during infusion in the VP group (mean dHbT=1.03, CI95=0.84, P=0.058; mean dHbO=0.92, CI95=0.91, P=0.071; mean dHb=0.10, CI95=0.21, P=0.297). The HbT and HbO showed a substantially smaller increase in the placebo group (mean dHbT=0.31, CI95=0.74,P=0.22; mean dHbO=0.57, CI95=0.80, P=0.094) while the Hb decreased (mean dHb=−0.26, CI95=0.29,P=0.05). Comparing to the placebo group Hb increased significantly in the VP group (P=0.027) while the increase of HbO and HbT did not reach the level of significance (P=0.29 and 0.11). DSI showed a significantly larger increase in the VP than in placebo group (dDSI=25.8 CI95=8.8 [VP]; dDSI=3.3, CI95=3.7 [Placebo], P<0.005). The CBFV and PI did not differ significantly between groups. (dVm=5.0±2.98 cm/s [VP], dVm=4.1±2.57 cm/s [Placebo], P=0.28; dPI=0.08 [VP], dPI=0.09 [Placebo]; P=0.47). Conclusion: VP increases cerebral perfusion and parenchymal oxygen extraction as well. The increased perfusion was indicated by NIRS and by TCD measurement of DSI while conventional velocity and pulsatility measurements failed to detect theses effects. NIRS is a sensitive, feasible method of measuring changes in regional blood flow and tissue oxygenation in the superficial cortex.
Citation: A double-blind placebo controlled evaluation of the safety and efficacy of vinpocetine in the treatment of patients with chronic vascular senile cerebral dysfunction. Balestreri, Roberto; Fontana, Luigi; Astengo, Federico Journal of the American Geriatrics Society, Vol 35(5), May 1987, 425-430.
Abstract: In a double-blind clinical trial, vinpocetine, a synthetic ethyl ester of apovincamine, was shown to effect significant improvement in 84 57–94 yr old patients with chronic cerebral dysfunction. 42 Ss received 10 mg vinpocetine 3 times a day (tid) for 30 days, then 5 mg tid for 60 days. Matching placebo tablets were given to another 42 Ss for the 90-day trial period. Ss on vinpocetine scored consistently better in all evaluations of the effectiveness of treatment including measurements on the Clinical Global Impression Scale, the Clinical Assessment-Geriatric Scale, and the Mini-Mental Status Questionnaire. No serious side effects were noted. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Abstract: HupA is a potent, reversible and selective inhibitor of AChE with a rapid absorption and penetration into the brain in animal tests. It exhibits memory-enhancing activities in animal and clinical trials. Compared to tacrine and donepezil, HupA possesses a longer duration of action and higher therapeutic index, and the peripheral cholinergic side effects are minimal at therapeutic doses. This review article deals with a comprehensive survey of the progress in chemical and pharmacological studies of HupA including the isolation and structure elucidation, pharmacological actions, total synthesis, SAR studies and the future development of HupA.
Recently, it has been reported that HupA could reduce neuronal cell death caused by glutamate. The dual bio-activities of HupA would further enhance its value and potentiality as the therapeutic agent for Alzheimers disease
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