ISPOR 22nd Annual International Meeting

The European ICTUS was a prospective observational cohort study involving patients with mild to moderate Alzheimer’s disease (MMSE 10-26 at baseline) from 29 hospital clinics in 11 European countries (Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Romania, Spain, Switzerland, UK). The long-term objective was to identify milestones in Alzheimer’s disease (AD) progression and to develop a model to predict disease course in individual AD patients.

In this analysis, AD progression was studied in 982 patients treated with acetylcholinesterase inhibitors in the European ICTUS study.

Data on four AD markers of Alzheimer’s disease measuring cognitive, behavioural and functional decline over the 2-year follow-up was analysed using multivariate regression modelling. The analysed AD markers were;

  • ADAS-cog – a subscale of ADAS (Alzheimer’s Disease Assessment Scale) designed to measure the severity of the most important symptoms of AD. The ADAS-cog measures cognitive domains including memory, language and praxis. Higher scores indicate greater cognitive impairment.
  • NPI – a validated informant-based interview that assess neuropsychiatric symptoms
  • over the previous month, including domains such as hallucinations, delusions, agitation, anxiety, irritability and apathy. A higher NPI score indicates more behavioural disturbance.
  • ADL – assess the patient’s ability to perform Activities of Daily Living (ADL).
  • IADL – the Instrumental Activities of Daily Living, situated between ADL scales and questionnaires measuring Quality of Life. IADL’s are activities related to independent living and include preparing meals, managing money, shopping for groceries or personal items, performing light or heavy housework, doing laundry, and using a telephone.

The model showed a strong multivariate relationship between the rate of change in cognition and functioning. The following correlations were found;

  • a faster rate of decline of ADL ßà higher IADL (rho=0.65)
  • a faster rate of decline of ADAS-cog ßà lower ADL (rho=-0.70)
  • a faster rate of decline of ADAS-cog ßà lower IADL (rho=-0.55)

ADAS-cog showed an annual increase of 4.55 [95%: 4.15,4.94; p<0.001], ADL a decrease of -0.49 [-0.54,-0.44; p<0.001] and IADL a decrease of -0.87 [-0.95,-0.79; p<0.001]. In other words, the AD patients showed a yearly increase in cognitive impairment and decrease in ability to perform activities of daily living.

This model analysis demonstrates the strength of correlation between cognition and function; providing an example of how to account for this within predictions. Whilst behaviour is also considered a conceptually important marker for AD progression; within this study it was not feasible to model all four markers simultaneously.

The abovementioned work will be presented by our co-author Owain Saunders at the ISPOR 22nd Annual Meeting in Boston, MA, USA, on 22 May 2017.

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