The current state of clinical trial methodology in Alzheimer's disease is discussed. With the development of regulatory guidelines and experience with cholinergic drugs in recent years there has been considerable progress in this field, especially with respect to the testing of symptomatic agents. As future research turns to examine compounds which may alter the progression of the disease, new methods need to be developed to allow this question to be studied. As well as washout designs using clinical instruments, there is the need to develop practical biological markers of the disease, such as magnetic resonance imaging scans and biochemical markers in the cerebrospinal fluid or plasma. Further considerations are also underway to design studies which could demonstrate a preventive effect of a compound in Alzheimer's disease, an important future treatment strategy.
LeberP.Guidelines for the clinical evaluation of antidementia drugs.1st Draft.Rockville, MD: US Food and Drug Administration; 1990.
2.
Committee for Proprietary Medicinal Products (CPMP) Note for Guidance on Medicinal Products in the Treatment of Alzheimer's Disease. London, UK: The European Agency for the Evaluation of Medicinal Products; 1998.
3.
MohrEFeldmanHGauthierS.Canadian Guidelines for the development of antidementia therapies: a conceptual summary. Can J Neurol Sci.1995;22: 62–71.
4.
TierneyMCFisherRHLewisAJThe NINCDSADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases. Neurology.1988;38:359–364.
5.
McKhannGDrachmanDFolsteinMClinical 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.
6.
American Psychiatric Association.Diagnostic and Statistical Manual of Mental Disorders.4th Edn.Washington, DC: American Psychiatric Association; 1994.
7.
FolsteinMFFolsteinSEMcHughPR“Mini-mental State“; a practical method for grading the conscious state of patients for the clinician. J Psychiat Res.1975;12:189–198.
8.
HamiltonM.Development of a rating scale for primary depressive illness. Brit J Soc Clin Psychol.1967;6:278–295.
9.
AlexopoulosGSAbramsRCYoungRCCornell Scale for depression in dementiaBiol Psychiatry.1988;23:271–284.
10.
RosenWGTerryRDFuldPAPathological verification of ischemic score in differentiation of dementiasAnn Neurol.1980;7:486–488.
11.
FontaineSNordbergA.Brain Imaging. In: Clinical Diagnosis and Management of Alzheimer's disease.GauthierS, ed. London: Martin Dunitz; 1996:83–105.
12.
RosenWGMohsRCDavisKLA new rating scale for Alzheimer's disease. Am J Psychiatry.1984;4: 1356–1364.
13.
SchneiderL.Validity and reliability of the Alzheimer's Disease Cooperative Study—Clinical Global Impression of Change (ADCS-CGIC). Alzheimer Dis Assoc Disord.1996.
LawtonMPInstrumental Activities of Daily Living (IADL) Scale. Psychopharmacol Bull.1988;24:785–787.
20.
GelinasG.Assessment of functional disability in Alzheimer's disease. Can J Occup Ther.1995;62(supp) 15.
21.
de JongR.Measurement of quality-of-life changes in patient with Alzheimer's disease. Clin Ther.1989;11:545–554.
22.
ReisbergBBorensteinJSalobSPBehavioral symptoms in Alzheimer's disease: phenomenology and treatment. J Clin Psychiatry.1987;48:9–15.
23.
BergLMillerJPMillerPBatyJRubinEHMorrisJCFigielG.Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention. Ann Neurol.1992;31:242–249.
24.
MohsR.Methodological Aspects of Evaluating Effects of AD Progression. Neurobiol Aging.1995;16(6):867–870.
25.
LeberP.Slowing the progression of the Alzheimer's disease—methodologic issues. Alzheimer's Dis Related Disorders.1997;11(Supp 5):S10–S20.
26.
SanoMErnestoCThomasRGKlauberMRSchaferKGrundmanMWoodburyPGrowdonJCotmanDWPfeifferESchneiderLSThalLJA controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. New Engl J Med.1997;336(17):1216–1222.
27.
KayeJASwihartTHowiesonDDameAMooreMMKarnonTCamicioliRBallMOkenBSextonG.Volume loss of the hippocampus and temporal lobe in healthy individuals destined to develop dementia. Neurology.1997;48:1297–1304.
28.
FoxNCFreeboroughPARossorMNVisualisation and quantification of rates of atrophy in Alzheimer's disease. Lancet.1996;348:94–97.
29.
BlombergMJensenMBasunHLannfeltLWahlundL-OIncrease of CSF tau levels in most Alzheimer patients during 15 month follow-up. Neurobiol Aging.1996;17:S167.
30.
KoivistoKPirtillaTMehtaKReinikainenKKimKSKilkuOHeinonenERiekkinenPWisniewskiHNLongitudinal study of CSF amyloid proteins and Apo E in patients with Alzheimer's disease. Neurobiol Aging.1996;17:S167.
31.
GauthierSThalLRossorM.The future diagnosis and treatment of Alzheimer's disease. In: Clinical Diagnosis and Management of Alzheimer's disease.GauthierS, ed. London: Martin Dunitz; 1996:359–365.
