Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia

Rai, G.S.; Wright, Gavin; Scott, L. C.; Beston, B.; Rest, Joan; Exton‐Smith, A. N.

doi:10.1185/03007999009112690

Cited by 71 publications

(30 citation statements)

References 14 publications

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“…No placebo group was included and the dose of LAC was smaller than the multiccntcr study (500 mg twice daily). Rai et al [119] found only a trend toward improvement (not statistically significant) on short-term memory tasks in a DBPC study of 20 patients, using 1.000 mg twice daily. Other reports, most of which are subsets of the large Italian trial, have found significant improvement in both depressive symp toms [ 120] and cognitive measures [121,122] using doses of 1.500-2.000 mg per day.…”

Section: L-acetyl Carnitinementioning

confidence: 94%

The Cholinergic Model of Dementia, Alzheimer Type: Progression from the Unitary Transmitter Concept

Holttum¹,

Gershon²

1992

Dement Geriatr Cogn Disord

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Efforts continue toward the goal of uncovering a dominant pathogenetic and therapeutic model for Alzheimer type dementia. This article critically reviews the evolution and current status of unitary transmitter concepts, the prototype of which is the cholinergic model proposed by Deutsch and others, from early animal studies to ongoing drug trials. We conclude that evidence is sufficient to dismiss such models as a means of directing treatment and further resources. A survey of novel approaches to Alzheimer type dementia, many of which transcend unitary thought, reveals a more promising direction for further research.

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Section: L-acetyl Carnitinementioning

confidence: 94%

The Cholinergic Model of Dementia, Alzheimer Type: Progression from the Unitary Transmitter Concept

Holttum¹,

Gershon²

1992

Dement Geriatr Cogn Disord

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“…Several clinical studies report the beneficial effects of ALCAR or LA:ALCAR administration in a small group of patients with AD that resulted in improved spatial orientation and short-term memory (24,25). LA administration in patients with AD for approximately 1 year also resulted in mild cognitive improvements and stabilization of global neuropsychological test scores (26).…”

mentioning

confidence: 99%

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- l -carnitine and/or R -α-lipoic acid

Liu

Head

Gharib

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

477

312

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Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-L-carnitine (ALCAR) [0.5% or 0.2% (wt͞vol) in drinking water], and͞or R-␣-lipoic acid (LA) [0.2% or 0.1% (wt͞wt) in diet]. Spatial memory was assessed by using the Morris water maze; temporal memory was tested by using the peak procedure (a time-discrimination procedure). Dietary supplementation with ALCAR and͞or LA improved memory, the combination being the most effective for two different tests of spatial memory (P < 0.05; P < 0.01) and for temporal memory (P < 0.05). Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2 -deoxyguanosine) increased with age in the hippocampus, a region important for memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of ALCAR and͞or LA significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that ALCAR and͞or LA reversed age-associated mitochondrial structural decay. These results suggest that feeding ALCAR and LA to old rats improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function.

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“…We suggest alternative goals for therapy, but are aware that few of them are directly assessed by neuropsychological tests, although some are assessed by rating scales. [35][36][37] Level 1, Class C Lecithin 38,39 Level 1, Class C Arecholine 40 Level 1, Class C Nimodipine 41 Level 1, Class C Velnacrine 42 Level 1, Class D Physostigmine [43][44][45] Level 1, Class D Eptastigmine 46 Level 1, Class D Phosphatidylserine 47 Level 1, Class D Memantine 48 Level 1, Class D 4 Aminopyridine (4AP) 49 Level 1, Class D Naloxone 50 Level 1, Class D Linopirdine 51 Level 1, Class D Aniracetam 52 Level 1, Class D Milacemide 53 Level 1, Class D Nicergolin 54 Level 1, Class D Idebenone 55 Level 1, Class D Huperzine-A 56 Level 1, Class D 5'-methyltetrahydrofolic acid 57 Level 1, Class D Desferrioxamine 58 Level 1, Class D Xantinolnicotinate 59 Level 1, Class D Bespirdine 60 Level 1, Class D Cycloserine 61 Level 1, Class D Cyclandelate 62 Level 1, Class D Thyrotropin 63 Level 1, Class D…”

Section: Discussionmentioning

confidence: 99%

The Use of Medications for Cognitive Enhancement

Pryse-Phillips

Sternberg

Rochon

et al. 2001

Can. J. Neurol. Sci.

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Objective:To provide Canadian physicians and allied health care professionals with the evidence they need to help them make treatment decisions in the management of patients with Alzheimer’s disease or other dementias.Options:The full range and quality of diagnostic and therapeutic modalities available to Canadian physicians for the management of dementia.Outcomes:Improvement in the treatment of dementias, leading to reduced suffering, increased functional capacity and decreased economic burden.Evidence and values:The creation of these evidence-based consensus statements involved literature reviews of the subject by the authors; comparison of alternative clinical pathways and description of the methods whereby published data were analyzed; definition of the level of evidence for data in each case; evaluation and revision in a conference setting (involving primary care physicians, neurologists, psychiatrists, geriatricians, psychologists, consumers and other interested parties); insertion of tables showing key variables and data from various studies and tables of data with recommendations; and reassessment by all authors.Benefits, harms, and costs:A rational plan for the therapy of dementias is likely to lead to substantial benefits in both human and economic terms.Recommendations:Treatment decisions should be made taking into account the severity or stage of the disease, the availability of caregivers, the presence of disease affecting other bodily systems and the ability of the subject to pay the cost of the medications. Donepezil is considered to have positive effects upon certain tests of neuropsychological function and may produce some improvement in Alzheimer’s disease of mild to moderate severity as measured by rating scales. Its ability to improve quality of life remains uncertain. No other drug treatments* (apart from symptomatic therapies) are at present approved for the treatment of Alzheimer’s disease.Validation:These recommendations were created by a writing committee, evaluated and revised at a consensus conference and further reviewed and revised by the writing committee prior to publication.

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Double-blind, placebo controlled study of acetyl-l-carnitine in patients with Alzheimer's dementia

Cited by 71 publications

References 14 publications

The Cholinergic Model of Dementia, Alzheimer Type: Progression from the Unitary Transmitter Concept

The Cholinergic Model of Dementia, Alzheimer Type: Progression from the Unitary Transmitter Concept

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- l -carnitine and/or R -α-lipoic acid

The Use of Medications for Cognitive Enhancement

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