Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: A multicenter, double-blind, randomized, placebo-controlled trial

      This paper is only available as a PDF. To read, Please Download here.


      Background: Parallel with the development of hypotheses regarding cholinergic involvement in geriatric memory dysfunction, the first attempts to treat patients with Alzheimer's disease (AD) involved the cholinergic-precursor loading approach. Despite encouraging early results, well-controlled clinical trials did not confirm a clinical utility of cholinergic precursors such as choline and lecithin (phosphatidylcholine) in AD.
      Objective: This study assessed the efficacy and tolerability of the cholinergic precursor choline alfoscerate (CA) in the treatment of cognitive impairment due to mild to moderate AD.
      Methods: In this multicenter, double-blind, randomized, placebo-controlled trial, patients affected by mild to moderate dementia of the Alzheimer type were treated with CA (400-mg capsules) or placebo capsules, 3 times daily, for 180 days. Efficacy outcome measures that were assessed at the beginning of the investigation and after 90 and 180 days of treatment included scores of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), the Mini-Mental State Examination (MMSE), the Global Deterioration Scale (GDS), the Alzheimer's Disease Assessment Scale-Behavioral Subscale (ADAS-Behav), all items of the Alzheimer's Disease Assessment Scale (ADAS-Total), and the Clinical Global Impression (CGI) scale. The Global Improvement Scale (GIS) score was assessed after 90 and 180 days of treatment.
      To read this article in full you will need to make a payment


      Subscribe to Clinical Therapeutics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bartus R.T
        • Dean III, R.L
        • Beer B
        • Lippa A.S
        The cholinergic hypothesis of geriatric memory dysfunction.
        Science. 1982; 217: 408-414
        • Larson E.B
        • Kukull W.A
        • Katzman R.L
        Cognitive impairment: Dementia and Alzheimer's disease.
        Annu Rev Public Health. 1992; 13: 431-449
        • Hofman A
        • Rocca W.A
        • Brayne C
        • et al.
        • for the European Prevalence Research Group
        The prevalence of dementia in Europe: A collaborative study of 1980–1990 findings.
        Int J Epidemiol. 1991; 20: 736-748
      1. Blackwood W Corsellis J.A.N Greenfield's Neuropathology. 3rd ed. Arnold, London1976
        • Geldmacher D.S
        Cost-effective recognition and diagnosis of dementia.
        Semin Neurol. 2002; 22: 63-70
        • Perry E.K
        • Tomlinson B.E
        • Blessed G
        • et al.
        Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia.
        BMJ. 1978; 2: 1457-1459
        • Perry E.K
        The cholinergic hypothesis—ten years on.
        Br Med Bull. 1986; 42: 63-69
        • Giacobini E
        From molecular structure to Alzheimer therapy.
        Jpn J Pharmacol. 1997; 74: 225-241
        • Giacobini E
        Invited review: Cholinesterase inhibitors for Alzheimer's disease therapy: From tacrine to future applications.
        Neurochem Int. 1998; 32: 413-419
        • Brinkman S.D
        • Smith R.C
        • Meyer J.S
        • et al.
        Lecithin and memory training in suspected Alzheimer's disease.
        J Gerontol. 1982; 37: 4-9
        • Davis E
        • Emmerling M.R
        • Jaen J.C
        • et al.
        Therapeutic intervention in dementia.
        Crit Rev Neurobiol. 1993; 7: 41-83
        • Amenta F
        • Parnetti L
        • Gallai V
        • Wallin A
        Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?.
        Mech Ageing Dev. 2001; 122: 2025-2040
        • Sigala S
        • Imperato A
        • Rizzonelli P
        • et al.
        l-Alpha-glycerylphosphorylcholine antagonizes scopolamine-induced amnesia and enhances hippocampal cholinergic transmission in the rat.
        Eur J Pharmacol. 1992; 211: 351-358
        • Govoni S
        • Battaini F
        • Lucchi L
        • et al.
        Effects of alpha-glycerylphosphorylcholine in counteracting drug-induced amnesia: Through cholinergic and non-cholinergic mechanisms [in Italian].
        Basi Raz Ter. 1991; 21: 75-78
        • Canonico P.L
        • Nicoletti F
        • Scapagnini U
        Neurochemical and behavioral effects of alpha-glycerylphosphorylcholine [in Italian].
        Basi Raz Ter. 1990; 20: 53-54
        • Parnetti L
        • Amenta F
        • Gallai V
        Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: An analysis of published clinical data.
        Mech Ageing Dev. 2001; 122: 2041-2055
        • Venn R.D
        The Sandoz Clinical Assessment-Geriatric (SCAG) scale. A general-purpose psychogeriatric rating scale.
        Gerontology. 1983; 29: 185-198
        • Di Perri R
        • Coppola G
        • Ambrosio L.A
        • et al.
        A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia.
        J Int Med Res. 1991; 19: 330-341
        • Frattola L
        • Piolti R
        • Bassi S
        • et al.
        Multicenter clinical comparison of the effects of choline alphoscerate and cytidine diphosphocholine in the treatment of multi-infarct dementia.
        Curr Ther Res Clin Exp. 1991; 49: 683-693
        • Muratorio A
        • Bonuccelli U
        • Nuti A
        • et al.
        A neurotropic approach to the treatment of multi-infact dementia using L-α-glycerylphosphorylcholine.
        Curr Ther Res Clin Exp. 1992; 52: 741-751
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.
        APA, Washington, DC1994
        • McKhann G
        • Drachman D
        • Folstein M
        • et al.
        Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease.
        Neurology. 1984; 34: 939-944
        • Folstein M.F
        • Folstein S.E
        “Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Loeb C
        • Gandolfo C
        Diagnostic evaluation of degenerative and vascular dementia.
        Stroke. 1983; 14: 399-401
        • Hamilton M
        A rating scale for depression.
        J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
        • Hamilton M
        Development of a rating scale for primary depressive illness.
        Br J Soc Clin Psychol. 1967; 6: 278-296
        • Rosen W.G
        • Mohs R.C
        • Davis K.L
        A new rating scale for Alzheimer's disease.
        Am J Psychiatry. 1984; 141: 1356-1364
        • Reisberg B
        • Ferris S.H
        • De Leon M.J
        • et al.
        The Global Deterioration Scale for assessment of primary degenerative dementia.
        Am J Psychiatry. 1982; 139: 1136-1139
        • National Institute of Mental Health
        Clinical global impressions.
        in: Guy W ECD-EU Assessment for Psychopharmacology. National Institute of Mental Health, Rockville, MD1976: 217-222 (Revised edition)
        • Burns A
        • Russell E
        • Page S
        New drugs for Alzheimer's disease.
        Br J Psychiatry. 1999; 174: 476-479
        • Kumar V
        • Anand R
        • Messina J
        • et al.
        An efficacy and safety analysis of Exelon in Alzheimer's disease patients with concurrent vascular risk factors.
        Eur J Neurol. 2000; 7: 159-169
        • Knapp M.J
        • Knopman D.S
        • Solomon P.R
        • et al.
        • for the Tacrine Study Group
        A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease.
        JAMA. 1994; 271: 985-991
        • Lindstrom M.J
        • Bates D.M
        Newton-Rapshon algorithms for linear-mixed effects models for repeated measure data.
        J Am Stat Assoc. 1998; 83: 1014-1022
        • Thal L.J
        • Carta A
        • Clarke W.R
        • et al.
        A 1-year multicenter placebo-controlled study of acetyl-l-carnitine in patients with Alzheimer's disease.
        Neurology. 1996; 47: 705-711
        • Rogers S.L
        • Friedhoff L.T
        • Donepezil Study Group
        The efficacy and safety of donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial.
        Dementia. 1996; 7: 293-303
        • Rogers S.L
        • Doody R.S
        • Mohs R.C
        • Friedhoff L.T
        • Donepezil Study Group
        Donepezil improves cognition and global function in Alzheimer disease: A 15-week, double-blind, placebo-controlled study.
        Arch Intern Med. 1998; 158: 1021-1031
        • Corey-Bloom J
        • Anand R
        • Veach J
        • ENA 713 B352 Study Group
        A randomized trial evaluating the efficacy and the safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease.
        Int J Geriatr Psychopharmacol. 1998; 1: 55-65
        • Rosler M
        • Anand R
        • Cicin-Sain A
        • et al.
        Efficacy and safety of rivastigmine in patients with Alzheimer's disease: International randomised controlled trial.
        BMJ. 1999; 318: 633-638
        • Amenta F
        • Bronzetti E
        • Del Valle M
        • Vega J.A
        Effects of alpha-glycerylphosphorylcholine in neuroanatomy of aging brain in experimental animals [in Italian].
        Basi Raz Ter. 1990; 20: 31-38