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LE Magazine July 2003

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GPC

Alpha-glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial.

The clinical efficacy and the tolerability of alpha-glycerophosphocholine (alpha-GPC), a drug able to provide high levels of choline for the nervous cells of the brain and to protect their cell walls, have been tested in a clinical open multicenter trial on 2044 patients suffering from recent stroke or transient ischemic attacks. alpha-GPC was administered after the attack at the daily dose of 1000 mg im for 28 days and orally at the dose of 400 mg tid during the following five months after the first phase. The evaluation of the efficacy on the psychic recovery was done by the Mathew Scale (MS) during the period of im drug administration, and using the Mini Mental State Test (MMST), the Crichton Rating Scale (CRS), and the Global Deterioration Scale (GDS) during the following period of oral administration. The MS mean increased 15.9 points in 28 days in a statistically significant way (p < 0.001) from 58.7 to 74.6. At the end of the five month oral administration, the CRS mean significantly decreased 4.3 points, from 20.2 to 15.9 (p < 0.001); the MMST mean significantly increased (p < 0.001) from 21 to 24.3 at the end of the trial, reaching the "normality" score at the 3rd month assessment. The GDS score at the end of the trial corresponded to "no cognitive decline" or "forgetfulness" in 71% of the patients. Forty-four patients complained of adverse events (2.14%); in 14 (0.7%) the investigator preferred to discontinue therapy. The most frequent complaints were heartburn (0.7%), nausea-vomit (0.5%), insomnia-excitation (0.4%), and headache (0.2%). The trial confirms the therapeutic role of alpha-GPC on the cognitive recovery of patients with acute stroke or TIA, and the low percentage of adverse events confirms its excellent tolerability.

Ann N Y Acad Sci 1994 Jun 30;717:253-69

Choline chloride fails to improve cognition of Alzheimer's disease.

Seven mildly- to moderately-demented patients with Alzheimer's disease were treated with either placebo or choline chloride (50, 100 and 200 mg/kg/24 hrs) in a double blind, crossover study. Detailed psychometric analysis was carried out at the end of each two-week period of drug or placebo administration. No subjects showed significant overall improvement at any dose level despite more than a doubling of the baseline plasma choline level.

Neurobiol Aging 1981 Fall;2(3):205-8

Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data.

This paper has reviewed the documentation on the clinical efficacy of choline alphoscerate, a cholinergic precursor, considered as a centrally-acting parasympathomimetic drug in dementia disorders and in acute cerebrovascular disease. Thirteen published clinical trials, examining in total 4,054 patients, have evaluated the use of choline alphoscerate in various forms of dementia disorders of degenerative, vascular or combined origin, such as senile dementia of the Alzheimer's type (SDAT) or vascular dementia (VaD) and in acute cerebrovascular diseases, such as transitory ischemic attack (TIA) and stroke. Analysis has assessed the design of each study, in particular with respect to experimental design, number of cases, duration of treatment and tests used to evaluate drug clinical efficacy. Most of the ten studies performed in dementia disorders were controlled trials versus a reference drug or placebo. Overall, 1,570 patients were assessed in these studies, 854 of which in controlled trials. As detected by validated and appropriate tests, such as Mini Mental State Evaluation (MMSE) in SDAT and Sandoz Clinical Assessment Geriatric (SCAG) in VaD, administration of choline alphoscerate significantly improved patient clinical condition. Clinical results obtained with choline alphoscerate were superior or equivalent to those observed in control groups under active treatment and superior to the results observed in placebo groups. Analysis stresses the clear internal consistency of clinical data gathered by different experimental situations on the drug effect, especially with regard to the cognitive symptoms (memory, attention) characterizing the clinical picture of adult-onset dementia disorders. The therapeutic usefulness of choline alphoscerate in relieving cognitive symptoms of chronic cerebral deterioration differentiates this drug from cholinergic precursors used in the past, such as choline and lecithin. Three uncontrolled trials were performed with choline alphoscerate in acute cerebrovascular stroke and TIA, totalling 2,484 patients. The results of these trials suggest that this drug might favor functional recovery of patients with cerebral stroke and should be confirmed in future investigations aimed at establishing the efficacy of the drug in achieving functional recovery of patients with acute cerebrovascular disease.

Mech Ageing Dev 2001 Nov;122(16):2041-55

Alpha-glycerylphosphorylcholine administration increases the GH responses to GHRH of young and elderly subjects.

Growth hormone (GH) secretion is decreased during aging in humans and in rodents. This decrease may be due to increased hypothalamic somatostatin release, which is inhibited by cholinergic agonists or to decreased secretion of GHRH. Alpha-glyceryl-phosphorylcholine (alpha-GFC) is a putative acetylcholine precursor used in the treatment of cognitive disorders in the elderly. In order to learn what effect alpha-GFC had on GH secretion, GH-release hormone (GHRH) was given to young and old human volunteers, with or without the addition of alpha-GFC. GH secretion was greater in the younger subjects than in the old individuals, and both groups had a greater GH response to the GHRH+alpha-GFC than to GHRH alone. The potentiating effect of alpha-GFC on GH secretion was more pronounced in the elderly subjects. These findings confirm the observation that aged individuals respond less well to GHRH than younger subjects, and provides further evidence that increased cholinergic tone enhances GH release.

Horm Metab Res 1992 Mar;24(3):119-21

Long-term choline alfoscerate treatment counters age-dependent microanatomical changes in rat brain.

1. The density of nerve cells and of silver-gold impregnated fibres were evaluated in the hippocampus and in the cerebellar cortex in adult (12-month-old) and old (24-month-old) Sprague-Dawley rats. 2. The effects of long-term choline alfoscerate (GFC) treatment (100 mg/Kg/day for six months) on the above parameters were investigated in old rats. 3. The number of nerve cell profiles and the area occupied by silver-gold impregnated fibres were decreased both in the hippocampus and in the cerebellar cortex in old in comparison with adult rats. 4. GFC treatment countered the age-dependent reduction of nerve cells and silver-gold impregnated fibres. The hippocampus was more sensitive than the cerebellar cortex to the activity of GFC. 5. These results suggest that GFC treatment is effective in slowing down the expression of structural changes occurring in aging brain.

Prog Neuropsychopharmacol Biol Psychiatry 1994 Sep;18(5):915-24

Prevalence of Alzheimer's disease and other dementias in rural India: the Indo-U.S. study.

OBJECTIVE: To determine the prevalence of Alzheimer's disease (AD) and other dementias in a rural elderly Hindi-speaking population in Ballabgarh in northern India. DESIGN: The authors performed a community survey of a cohort of 5,126 individuals aged 55 years and older, 73.3% of whom were illiterate. Hindi cognitive and functional screening instruments, developed for and validated in this population, were used to screen the cohort. A total of 536 subjects (10.5%) who met operational criteria for cognitive and functional impairment and a random sample of 270 unimpaired control subjects (5.3%) underwent standardized clinical assessment for dementia using the Diagnostic and Statistical Manual of Mental Disorders-fourth edition diagnostic criteria, the Clinical Dementia Rating Scale (CDR), and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable and possible AD. RESULTS: We found an overall prevalence rate of 0.84% (95% CI, 0.61 to 1.13) for all dementias with a CDR score of at least 0.5 in the population aged 55 years and older, and an overall prevalence rate of 1.36% (95% CI, 0.96 to 1.88) in the population aged 65 years and older. The overall prevalence rate for AD was 0.62% (95% CI, 0.43 to 0.88) in the population aged 55+ and 1.07% (95% CI, 0.72 to 1.53) in the population aged 65+. Greater age was associated significantly with higher prevalence of both AD and all dementias, but neither gender nor literacy was associated with prevalence. CONCLUSIONS: In this population, the prevalence of AD and other dementias was low, increased with age, and was not associated with gender or literacy. Possible explanations include low overall life expectancy, short survival with the disease, and low age-specific incidence potentially due to differences in the underlying distribution of risk and protective factors compared with populations with higher prevalence.

Neurology 1998 Oct;51(4):1000-8

Classification criteria for mild cognitive impairment: a population-based validation study

OBJECTIVE: To evaluate the predictive validity and temporal stability of diagnostic criteria for mild cognitive impairment (MCI). BACKGROUND: MCI has been proposed as a nosologic entity referring to elderly persons with subclinical cognitive deficits due to incipient dementia. Classification criteria, which have been derived from small, selected clinical groups, are currently disputed, and have not yet been assessed within the general population. METHODS: Subjects meeting current criteria for MCI and also age-associated cognitive decline (AACD-a similar concept that is assumed to be related to normal cognitive aging processes rather than incipient dementia) were identified within each of three waves of a longitudinal population study, which included a standardized neurologic examination. RESULTS: In the general population, the prevalence of MCI was estimated to be 3.2% and AACD 19.3%. MCI was a poor predictor of dementia within a 3-year period, with an 11.1% conversion rate. Subjects with MCI also constituted an unstable group, with almost all subjects changing category each year. Discriminant function analysis failed to isolate a homogeneous clinical group. Subjects classified as AACD, contrary to the theoretical assumptions underlying the disorder, represented a more stable group, with a 28.6% conversion rate to dementia over three years (relative risk = 21.2). CONCLUSION: MCI criteria perform poorly when applied to a representative population sample. The authors propose modifications to current diagnostic criteria to increase their capacity to detect incipient dementia.

Neurology 2001 Jan 9;56(1):37-42

Current concepts in mild cognitive impairment.

The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

Arch Neurol 2001 Dec;58(12):1985-92

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