title: Predicting the outcome of cholinesterase inhibitor treatment in Alzheimer's disease.
abstract: OBJECTIVE
  To investigate the possibility that response to cholinesterase inhibitor therapy could be predicted by easily measurable variables that are known to change as a result of treatment (such as the Mini Mental State Examination), measures of function (such as the instrumental activities of daily living and the social behaviour subscales of the Nurse's Observation Scale for Geriatric Patients), and measures of attention (such as the Digit Symbol Substitution Test; DSST), or that might influence response through structural (for example, age, cerebrovascular disease, medial temporal lobe (MTL) atrophy, hypertension) or chemical (for example, smoking) mechanisms.
  
  
  METHODS
  This was a cohort study of 160 consecutive outpatients with probable Alzheimer's disease who commenced cholinesterase inhibitor treatment over a 3 year period in a semi-rural area of Scotland.
  
  
  RESULTS
  The overall response rate was 42.1%. Stratification of response between good and poor responders was possible using baseline DSST and a measure of MTL thickness using CT. Among the patients, 60.4% of those above the cut off point for both DSST and MTL thickness (29/48 subjects) were classified as good responders, compared with 6.3% of subjects below the cut off point for both (1/16 subjects). Subjects above the cut off point for both measures were more likely to be classified as good responders than subjects with only one or no values above the respective cut off points (chi(2) = 10.61, df = 1, p = 0.001)
  
  
  CONCLUSIONS
  The DSST and a measure of MTL thickness derived from CT scanning may be useful in improving the prediction of response to cholinesterase inhibitors in subjects with AD. Subjects with low DSST scores and more severe MTL atrophy are unlikely to respond to treatment. These preliminary data justify a prospective trial of the usefulness of our suggested predictive measures.
authors.affiliation: Department of Psychiatry, University of Dundee, Murray Royal Hospital, Muirhall Road, Perth, PH2 7BH, UK. pjc@dementiaresearch.freeserve.co.uk
authors.forename: P J
authors.initials: PJ
authors.lastname: Connelly
authors.forename: N P
authors.initials: NP
authors.lastname: Prentice
authors.forename: K G
authors.initials: KG
authors.lastname: Fowler
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D015331:Cohort Studies; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D009730:Nursing Assessment; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors
references.citation: Ann Neurol. 1980 May;7(5):486-8
references.pmid: 7396427
references.citation: Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12260-4
references.pmid: 8618881
references.citation: Arch Neurol. 1988 Jun;45(6):637-41
references.pmid: 3259421
references.citation: J Am Geriatr Soc. 1991 Apr;39(4):339-47
references.pmid: 2010583
references.citation: Arch Neurol. 1992 Jun;49(6):626-32
references.pmid: 1596198
references.citation: Neuropsychobiology. 1992;25(1):24-8
references.pmid: 1603291
references.citation: Lancet. 1992 Nov 14;340(8829):1179-83
references.pmid: 1359259
references.citation: Dementia. 1993 Jan-Feb;4(1):54-8
references.pmid: 8358507
references.citation: Psychopharmacology (Berl). 1993;110(4):395-401
references.pmid: 7870908
references.citation: Int J Geriatr Psychiatry. 2000 Jan;15(1):50-3
references.pmid: 10637404
references.citation: Eur J Neurol. 2000 Mar;7(2):159-69
references.pmid: 10809936
references.citation: Methods Find Exp Clin Pharmacol. 2000 Mar;22(2):115-22
references.pmid: 10849895
references.citation: Neurology. 2000 Jun 27;54(12):2261-8
references.pmid: 10881250
references.citation: Neurology. 2000 Jun 27;54(12):2269-76
references.pmid: 10881251
references.citation: J Neurol Neurosurg Psychiatry. 1996 Apr;60(4):431-6
references.pmid: 8774411
references.citation: Neuroreport. 1997 May 27;8(8):1845-9
references.pmid: 9223063
references.citation: Int J Geriatr Psychiatry. 1998 Oct;13(10):661-6
references.pmid: 9818300
references.citation: BMJ. 1999 Mar 6;318(7184):633-8
references.pmid: 10066203
references.citation: Dement Geriatr Cogn Disord. 1999 May-Jun;10(3):237-44
references.pmid: 10325453
references.citation: Int Psychogeriatr. 2000 Jun;12(2):231-47
references.pmid: 10937543
references.citation: Int J Geriatr Psychiatry. 2000 Aug;15(8):713-20
references.pmid: 10960883
references.citation: Dement Geriatr Cogn Disord. 2000 Sep;11 Suppl 1:19-27
references.pmid: 10971048
references.citation: Dement Geriatr Cogn Disord. 2001 Jan-Feb;12(1):22-32
references.pmid: 11125238
references.citation: Dement Geriatr Cogn Disord. 2001 Mar-Apr;12(2):69-77
references.pmid: 11173877
references.citation: Arch Neurol. 2001 Mar;58(3):417-22
references.pmid: 11255445
references.citation: Neurology. 2001 Aug 14;57(3):489-95
references.pmid: 11502918
references.citation: Int J Geriatr Psychiatry. 2001 Sep;16(9):837-45
references.pmid: 11571761
references.citation: Age Ageing. 2003 Mar;32(2):200-4
references.pmid: 12615565
references.citation: Int J Geriatr Psychiatry. 2003 Apr;18(4):308-12
references.pmid: 12673606
references.citation: Dement Geriatr Cogn Disord. 2003;16(3):119-25
references.pmid: 12826736
references.citation: J Neurol Neurosurg Psychiatry. 2004 Feb;75(2):292-4
references.pmid: 14742608
references.citation: Br J Psychiatry. 1969 Mar;115(520):267-71
references.pmid: 5794120
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Psychopharmacology (Berl). 1995 Mar;118(1):82-92
references.pmid: 7597126
references.citation: Arch Neurol. 1995 Jul;52(7):659-64
references.pmid: 7619020
references.citation: Neuroreport. 1995 Jun 19;6(9):1297-300
references.pmid: 7669991
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841