Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease

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.

[1]  M. Alberoni,et al.  Long‐term acetyl‐L‐carnitine treatment in Alzheimer's disease , 1991, Neurology.

[2]  R F Woolson,et al.  A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer's disease. The Tacrine Collaborative Study Group. , 1992, The New England journal of medicine.

[3]  David M. A. Mann,et al.  The neuropathology of Alzheimer's disease: A review with pathogenetic, aetiological and therapeutic considerations , 1985, Mechanisms of Ageing and Development.

[4]  G. Taglialatela,et al.  Acetyl-l-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats , 1994, Experimental Gerontology.

[5]  L. Sokoloff.  Function-related changes in energy metabolism in the nervous system: localization and mechanisms. , 1993, The Keio journal of medicine.

[6]  F. Buonanno,et al.  In Vitro31P NMR Spectroscopy Detects Altered Phospholipid Metabolism in Alzheimer's Disease , 1986, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[7]  J. Pettegrew.  Molecular Insights into Alzheimer's Disease , 1989, Annals of the New York Academy of Sciences.

[8]  N. Campi,et al.  Selegiline versus L-acetylcarnitine in the treatment of Alzheimer-type dementia. , 1990, Clinical therapeutics.

[9]  M Farlow,et al.  A controlled trial of tacrine in Alzheimer's disease. The Tacrine Study Group. , 1992, JAMA.

[10]  Joseph B. Martin,et al.  Phosphoethanolamine and ethanolamine are decreased in Alzheimer's disease and Huntington's disease , 1987, Brain Research.

[11]  R. Zec,et al.  Alzheimer Disease Assessment Scale: Useful for Both Early Detection and Staging of Dementia of the Alzheimer Type , 1992, Alzheimer disease and associated disorders.

[12]  M. Keshavan,et al.  Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics. A pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy. , 1991, Archives of general psychiatry.

[13]  D. Cucinotta,et al.  Multicentre Study of l-α-Glyceryl-Phosphorylcholine vs ST200 among Patients with Probable Senile Dementia of Alzheimer’s Type , 1993, Drugs & aging.

[14]  M. Calvani,et al.  Clues to the Mechanism of Action of Acetyl-L-Carnitine in the Central Nervous System , 1991 .

[15]  H. Yeh,et al.  Detection of NGF-like activity in human brain tissue: increased levels in Alzheimer's disease , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  N. Minshew,et al.  31P Nuclear Magnetic Resonance Studies of Phosphoglyceride Metabolism in Developing and Degenerating Brain: Preliminary Observations , 1987, Journal of neuropathology and experimental neurology.

[17]  W. Markesbery,et al.  31P magnetic resonance spectroscopy in alzheimer's and pick's disease , 1993, Neurobiology of Aging.

[18]  E. Mufson,et al.  Loss of nerve growth factor receptor-containing neurons in Alzheimer's disease: A quantitative analysis across subregions of the basal forebrain , 1989, Experimental Neurology.

[19]  L. Sokoloff,et al.  Measurement of local cerebral glucose utilization and its relation to local functional activity in the brain. , 1991, Advances in experimental medicine and biology.

[20]  J. Growdon,et al.  Evidence for a membrane defect in Alzheimer disease brain. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[21]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[22]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[23]  E. Masliah,et al.  The synaptic organization of the neocortex in Alzheimer's disease. , 1993, Medical hypotheses.

[24]  B Carragher,et al.  Three-Dimensional Analysis of the Relationship Between Synaptic Pathology and Neuropil Threads in Alzheimer Disease , 1992, Journal of neuropathology and experimental neurology.

[25]  K. Marder,et al.  Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. , 1992, Archives of neurology.

[26]  J. Pettegrew,et al.  Alterations of cerebral metabolism in probable Alzheimer's disease: A preliminary study , 1994, Neurobiology of Aging.

[27]  J. Pettegrew,et al.  31P Nuclear Magnetic Resonance Study of the Brain in Alzheimer's Disease , 1988, Journal of neuropathology and experimental neurology.

[28]  A. Miccheli,et al.  Aging brain: effect of acetyl-l-carnitine treatment on rat brain energy and phospholipid metabolism. A study by31P and1H NMR spectroscopy , 1990, Brain Research.