[Solution]Treating Alzheimer’s disease

A new pharmacological compound, compound A, has been developed as a potential therapy to treat Alzheimer’s disease. The purpose of this randomised, double-blind study at…

A new pharmacological compound, compound A, has been developed as a potential therapy to treat Alzheimer’s disease.

The purpose of this randomised, double-blind study at one research centre was to determine the effect of compound A on neuron degeneration in the brains of people with Alzheimer’s disease.

The study consisted of 53% female and 47% male participants. The age range of participants was 61 – 84 years old. No information was given about the ethnicity of the participants.

20mg or 40mg of compound A in tablet form, or a placebo tablet, was taken by the participants orally, daily for 6 months. Participants were randomly assigned to treatment groups.

Details of the group participants are shown in Table 1:

Treatment groupNumber of participantsMean number of years since diagnosisPlacebo3053.1Compound A 20mg2852.9Compound A 40mg923.2

Table 1. Number of participants and the mean number of years since diagnosis of Alzheimer’s disease, in each treatment group.

Neuron degeneration was measured in the participants both before and after the 6 months of treatment, using magnetic resonance imaging (MRI) analysis of participants brains.

The size of a specific area of the frontal lobe was measured using the MRI images from each participant. The size of this specific area correlates with the number of living neurons in this area; this makes this a good way to estimate neuron degeneration. In Alzheimer’s patients, the size of this area is reduced, due to the loss of neurons which have degenerated and died.

Question 1 continued…

MRI results are shown below in table 2:

Treatment groupSize of specific frontal lobe area (mm3)  p value vs. ‘Before treatment’ of the same groupp value vs. ‘After 6 months treatment’ of Placebo groupBefore treatmentAfter 6 months treatmentPlacebo95.6 ± 1.563.2 ± 2.6*–Compound A 20mg93.3 ± 1.178.2 ± 1.2**Compound A 40mg96.1 ± 0.576.2  ± 2.1**

Table 2. MRI image results before and after 6-months treatment with placebo or 20mg / 40mg compound. The size of the specific measured frontal lobe using MRI is shown. Results are expressed as mean ± S.E.M.  *  p < 0.05, Student’s paired t-test.

(5 marks)

(1 mark)

Describe the main conclusions you can make from this data.

(4 marks)

A further investigation into compound A’s efficacy was then carried out by testing all the participants’ frontal lobe function, using the Wisconsin Card Sorting Test, after the 6 months treatment with compound A or placebo. A higher number of perseverative errors indicates worse frontal lobe function. Results are shown in table 3 below:

Question 1 continued…

Treatment groupNumber of perseverative errors p value vs. PlaceboPlacebo4.2 ± 0.5 –Compound A 20mg3.9 ± 0.6 n.s.Compound A 40mg4.1 ± 0.4 n.s.

Table 3. Number of perseverative errors made in the Wisconsin Card Sorting Test by participants from the three treatment groups after 6 months treatment. Results are expressed as mean ± S.E.M.  *  p < 0.05; n.s. = not significant; Student’s t-test.

(2 marks)

(3 marks)

The physicochemical properties of compound A, and an alternative but similar compound B, are shown in table 4 below:

 Compound ACompound BHydrogen bond acceptors312Hydrogen bond donors28Molecular mass (Da)184644Log P3.54.9

Table 4. Physiocochemical properties of compounds A and B.

Using the data in table 4, which compound (A or B) would be a better choice for treating Alzheimer’s disease?

(2 marks)

Suggest some further work that could be done, to assess in more detail whether compound A could be a useful treatment for Alzheimer’s disease.
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