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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: [email protected]
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Abstract:

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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

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