Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-18T14:22:43.578Z Has data issue: false hasContentIssue false
  • English
  • Français

Cognitive Change in Donepezil Treated Patients with Vascular or Mixed Dementia

Published online by Cambridge University Press:  23 September 2014

Kenneth Rockwood ,
Arnold Mitnitski ,
Sandra E. Black ,
Matthew Richard  and
Isabelle Defoy
Kenneth Rockwood*
Affiliation:
DGI Clinical Inc., Dalhousie University, Halifax, Nova Scotia Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia
Arnold Mitnitski
Affiliation:
DGI Clinical Inc., Dalhousie University, Halifax, Nova Scotia Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia
Sandra E. Black
Affiliation:
Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario
Matthew Richard
Affiliation:
DGI Clinical Inc., Dalhousie University, Halifax, Nova Scotia
Isabelle Defoy
Affiliation:
Pfizer Canada Inc., Kirkland, Quebec, Canada
*
DGI Clinical Inc., Suite 208, 1344 Summer Street, Halifax, Nova Scotia, B3H 0A8, Canada. Email: krockwood@dgiclinical.com
Rights & Permissions [Opens in a new window]

Abstract:

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

vascular dementia (VaD) and mixed Alzheimer's disease (AD/VaD) are common. How best to monitor treatment is not clear. Our objective was to compare responsiveness and construct validity of change scores, following donepezil treatment, of the standardized Mini-Mental State Examination (sMMSE) and other measures potentially usable in primary care.

Methods:

A six-month, outcome measurement study. The Disability Assessment for Dementia (DAD), CLOX-1 and 2, Phonetic Fluency, a short Neuropsychiatric Inventory, (the NPI-Q), Clinical Global Impression (CGI) and the SymptomGuide™ (SG) were measured. Construct validity was tested by correlating change scores, and responsiveness by calculating standardized response means (SRMs).

Results:

Of 148 treated patients, 116 completed. The mean sMMSE increased by 0.7 (95% Confidence Interval (CI) = -0.005, 1.41; p=0.06; SRM= 0.15). There was no statistically significant difference in the DAD. The NPI-Q (-1.4; 95% CI = -2.08, -0.72; p<0.01; SRM=0.24), ClOX-1 (0.9; 95% CI = 0.19, 1.61; p<0.01; SRM=0.21), ClOX-2 (0.9; 95% CI = 0.17, 1.63; p=0.03; SRM=0.26), Phonetic Fluency (0.9; 95% CI = 0.19, 1.61; p=0.02; SRM=0.21) and SG (0.35; 95% CI = 0.20,0.51; p<0.01; SRM=0.28) each detected significant improvement. The CGI suggested improvement in 74 completers (64%) - mostly “minimal” (44/116, 38%) - while 21/116 (18%) were worse. Change scores at 24 weeks were at best modestly correlated with each other (range -0.22 to 0.30).

Discussion:

Different measures showed different responsiveness, in a setting in which the mean treatment effect seems to have been small, but clinically detectable. Patient-centered and executive function measures might be useful in vascular and mixed dementia.

Résumé:

RÉsumÉ:Contexte:

La démence vasculaire (DV) et la maladie d'Alzheimer mixte (MA/DV) sont des maladies fréquentes. Toutefois, on ne connaît pas quelle est la meilleure façon de faire le suivi de ces patients au cours du traitement. Le but de notre étude était de comparer la réactivité et la validité conceptuelle des taux de changement observés au mini examen de l'état mental (MMSE) et à d'autres instruments de mesure utilisables dans les soins de première ligne, suite au traitement par le donépézil.

Méthode:

Nous avons effectué une étude des résultats obtenus après six mois de traitement. Nous avons utilisé l'échelle d'évaluation de l'invalidité associée à la démence (DAD), les tests du cadran de l'horloge CLOX-1 et 2, le test de la fluence verbale phonologique (TFVP), un inventaire neuropsychiatrique abrégé, le NPI-Q, le test d'impression clinique globale CGI et le Guide des symptômes (GS). la validité conceptuelle a été évaluée au moyen de la corrélation des scores de changement et la réponse au traitement a été évaluée par le calcul des moyennes des réponses standardisées (MRS).

Résultats:

Parmi les 148 patients traités, 116 ont complété les évaluations. la moyenne au MMSE a augmenté de 0,7 (IC à 95% : -0,005 à 1,41; p = 0,06; MRS = 0,15). Nous n'avons pas noté de différence significative au point de vue statistique pour le DAD. le NPI-Q (-1,4; IC à 95% : -2,08 à -0,72; p < 0,01; MRS 0,24), le CLOX-1 (0,9; IC à 95% : 0,19 à 1,61; p < 0,01; MRS 0,21), le ClOX-2 (0,9; IC à 95%: 0,17 à 1,63; p = 0,03; MRS = 0,26), le TFVP (0,0 IC à 95% : 0,19 à 1,61; p = 0,02; MRS = 0,21) et GS (0,35; IC à 95% : 0,20 à 0,51; < 0,01; MRS = 0,28) ont tous détecté une amélioration significative. le CGI suggérait une amélioration chez 74 sujets (64%) et cette amélioration était minime (44/116, 38%), alors que 21/116 étaient pires (18). les scores de changement à 24 semaines étaient au mieux corrélés faiblement entre eux (écart de -0,22 à 0,30).

Discussion:

Différentes mesures ont montré une réactivité différente dans le contexte d'un effet moyen du traitement qui semble avoir été faible mais détectable au point de vue clinique. Des mesures centrées sur le patient et des mesures de la fonction exécutive pourraient être utiles dans la démence vasculaire et la démence mixte.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 40 , Issue 4 , July 2013 , pp. 564 - 571
Copyright
Copyright © The Canadian Journal of Neurological 2013

References

1. Moorhouse, P, Rockwood, K. Vascular cognitive impairment: current concepts and clinical developments. Lancet Neurol. 2008;7:246–55.CrossRefGoogle ScholarPubMed
2. Gorelick, PB, Scuteri, A, Black, SE, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:2672–713.CrossRefGoogle ScholarPubMed
3. Román, GC, Tatemichi, TK, Erkinjuntti, T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDSAIREN International Workshop. Neurology. 1993;43:250–60.CrossRefGoogle ScholarPubMed
4. Wang, BW, Lu, E, Mackenzie, IR, et al. Multiple pathologies are common in Alzheimer patients in clinical trials. Can J Neurol Sci. 2012;39(5):592–9.CrossRefGoogle ScholarPubMed
5. Snowdon, DA, Greiner, LH, Mortimer, JA, Riley, KP, Greiner, PA, Markesbery, WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA 1997;277:813–7.Google ScholarPubMed
6. Neuropathology, Group. Medical Research Council Cognitive Function and Aging Study. Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS). Lancet. 2001;357:169–75.Google Scholar
7. launer, LJ, Petrovitch, H, Webster, RG, Markesbery, W, White, LR. AD brain pathology: vascular origins? Results from the HAAS autopsy study. Neurobiol Aging. 2008;29:1587–90.Google Scholar
8. Shi, GX, Liu, CZ, Wang, LP, Guan, LP, Li, SQ. Biomarkers of oxidative stress in vascular dementia patients. Can J Neurol Sci. 2012;39(1):65–8.Google Scholar
9. Perry, G, Phelix, CF, Nunomura, A, et al. Untangling the vascular web from Alzheimer disease and oxidative stress. Can J Neurol Sci. 2012;39(1):4.CrossRefGoogle ScholarPubMed
10. Birks, J. The evidence for the efficacy of cholinesterase inhibitors in the treatment of Alzheimer’s disease is convincing. Int Psychogeriatr. 2008;20:1–7.Google Scholar
11. Erkinjuntti, T, Roman, G, Gauthier, S, Feldman, H, Rockwood, K. Emerging therapies for vascular dementia and vascular cognitive impairment. Stroke. 2004;35:1010–17.Google Scholar
12. Wong, CL, Bansback, N, Lee, PE, Anis, AH. Cost-effectiveness: cholinesterase inhibitors and memantine in vascular dementia. Can J Neurol Sci. 2009;36(6):735–9.Google Scholar
13. Wilkinson, D, Doody, R, Helme, R, et al. Donepezil in vascular dementia: a randomized, placebo-controlled study. Neurology. 2003;61:479–86.CrossRefGoogle ScholarPubMed
14. Black, S, Román, GC, Geldmacher, DS, et al. Donepezil 307 vascular Dementia Study Group. Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial. Stroke. 2003;34:2323–30.Google Scholar
15. Mohs, RC, Knopman, D, Petersen, RC, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer’s Disease Assessment Scale that broaden its scope. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11(suppl 2):S13–21.CrossRefGoogle Scholar
16. Román, GC, Salloway, S, Black, SE, et al. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential effects by hippocampal size. Stroke. 2010;41:1213–21.Google Scholar
17. Gauthier, S, Patterson, C, Chertkow, H, et al. Recommendations of the 4th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4). Can Geriatr J. 2012 Dec;15(4):120–6.Google Scholar
18. Levine, DA, Langa, KM. Vascular cognitive impairment: disease mechanisms and therapeutic implications. Neurotherapeutics. 2011;8:361–73.Google Scholar
19. Gauthier, S, Ferris, S. Outcome measures for probable vascular dementia and Alzheimer’s disease with cerebrovascular disease. Int J Clin Pract Suppl. 2001;(120):29–39.Google Scholar
20. Winblad, B, Engedal, K, Soininen, H, et al. A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology. 2001;57:489–95.Google Scholar
21. Román, GC, Wilkinson, DG, Doody, RS, Black, SE, Salloway, SP, Schindler, RJ. Donepezil in vascular dementia: combined analysis of two large-scale clinical trials. Dement Geriatr Cogn Disord. 2005;20:338–44.Google Scholar
22. American Psychiatric Association. Diagnostic and Statistical Manual. 4th ed., text rev. Washington: American Psychiatric Association; 2005.Google Scholar
23. Hachinski, VC, Iliff, LD, Zilhka, E, et al. Cerebral blood flow in dementia. Arch Neurol. 1975;32:632–7.Google Scholar
24. Reisberg, B. Functional assessment staging (FAST). Psychopharmacol Bull. 1988;24:653–9.Google Scholar
25. Rockwood, K, Black, SE, Song, X, et al. Clinical and radiographic subtypes of vascular cognitive impairment in a clinic-based cohort study. J Neurol Sci. 2006;240(1-2):7–14.Google Scholar
26. Hamilton, M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56–62.Google Scholar
27. Molloy, DW, Standish, TI. A guide to the standardized Mini-Mental State Examination. Int Psychogeriatr. 1997;9(Suppl 1):87–94; discussion 143-50.Google Scholar
28. Gélinas, I, Gauthier, L, McIntyre, M, Gauthier, S. Development of a functional measure for persons with Alzheimer’s disease: the disability assessment for dementia. Am J Occup Ther. 1999 Sep-Oct;53(5):471–81.CrossRefGoogle ScholarPubMed
29. Royall, DR, Cordes, JA, Polk, M. CLOX: an executive clock drawing task. J Neurol Neurosurg Psychiatry. 1998;64:588–94.CrossRefGoogle ScholarPubMed
30. Gladsjo, JA, Schuman, CC, Evans, JD, Peavy, GM, Miller, SW, Heaton, RK. Norms for letter and category fluency: demographic corrections for age, education, and ethnicity. Assessment. 1999;147–78.Google Scholar
31. Kaufer, DI, Cummings, JL, Ketchel, P, et al. Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. J Neuropsychiatry Clin Neurosci. 2000;12:233–9.Google Scholar
32. Rockwood, K. An individualized approach to tracking and treating Alzheimer’s disease. Clin Pharmacol Ther. 2010;88:446–9.Google Scholar
33. Molnar, FJ, Man-Son-Hing, M, Fergusson, D. Systematic review of measures of clinical significance employed in randomized controlled trials of drugs for dementia. J Am Geriatr Soc. 2009;57:536–46.Google Scholar
34. Molnar, FJ, Man-Son-Hing, M, Hutton, B, Fergusson, DA. Have last-observation-carried-forward analyses caused us to favour more toxic dementia therapies over less toxic alternatives? A systematic review. Open Med. 2009;3(2):e31–50.Google ScholarPubMed
35. Little, RJ, D’Agostino, R, Cohen, ML, et al. The prevention and treatment of missing data in clinical trials. N Engl J Med. 2012;367(14):1355–60.Google Scholar
36. Liang, MH, Fossel, AH, Larson, MG. Comparisons of five health status instruments for orthopedic evaluation. Med Care. 1990;28:632–42.Google Scholar
37. Cohen, J. Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Englewood Cliffs: Lawrence Erlbaum Associates; 1988.Google Scholar
38. Rockwood, K. Size of the treatment effect on cognition of cholinesterase inhibition in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2004;75(5):677–85.Google Scholar
39. Moorhouse, P, Song, X, Rockwood, K, et al., Executive dysfunction in vascular cognitive impairment in the consortium to investigate vascular impairment of cognition study. J Neurol Sci. 2010;288:142–6.Google Scholar
40. Rockwood, K. Should we listen to people affected by dementia? CNS Neurosci Ther. 2011;17 (1):1–3.Google Scholar
41. Ballard, C, Gauthier, S, Corbett, A, Brayne, C, Aarsland, D, Jones, E. Alzheimer’s disease. Lancet. 2011;377(9770):1019–31.Google Scholar
42. Rockwood, K, Black, SE, Robillard, A, Lussier, I. Potential treatment effects of donepezil not detected in Alzheimer’s disease clinical trials: a physician survey. Int J Geriatr Psychiatry. 2004;19(10):954–60.Google Scholar
43. Behl, P, Lanctôt, KL, Streiner, DL, Black, SE. The effect of cholinesterase inhibitors on decline in multiple functional domains in Alzheimer’s disease: a two-year observational study in the Sunnybrook dementia cohort. Int Psychogeriatr. 2008;20:1141–59.Google Scholar
44. Gillette-Guyonnet, S, Andrieu, S, Nourhashemi, F, et al. REAL.FR study group. Long-term progression of Alzheimer’s disease in patients under antidementia drugs. Alzheimers Dement. 2011;7(6):579–92.CrossRefGoogle Scholar