Putting Alzheimer’s disease to the test: Improving pharmaceutical development and patient outcomes
Posted on 11 May 2015 in Clinical Trials / Healthcare / Research
Author: Barbara Sahakian
Senior Consultant, Professor of Clinical Neuropsychology, University of Cambridge and Co-creator of Cantab
Very few people will not have their lives touched by Alzheimer’s disease in some way. Almost everyone will have a close relative or friend who has suffered from the disease. In the UK alone, there are 850,000 people with dementia1; 1 in every 14 of the population aged 65 years and over. In addition to the toll that Alzheimer’s disease takes on individuals, their family members and society, it is also very expensive for Governments.
Alzheimer’s disease and other dementias are a huge and growing public health problem, affecting 36 million people worldwide and costing more than US$600 billion a year2. In this blog post, I will describe my work developing sensitive assessments of cognition for patients with Alzheimer’s disease, and the application of these tests in academic research, pharmaceutical clinical trials and healthcare settings.
At the early stages of Alzheimer’s disease, the first signs are cognitive ones, and these are relatively restricted to memory problems before progressing to other forms of cognition. This reflects the damage in the brain, which starts in areas such as the hippocampus and temporal lobes, and progresses in a forwards direction to other brain regions including frontal cortex.
Sensitive assessments for Alzheimer's disease
In the late 1980s, I was working as a Clinical Neuropsychologist in one of the first Memory Clinics established in the UK. To my disappointment, the cognitive tools we had for assessing memory problems were insensitive to the early stages of Alzheimer’s disease. Therefore, I became very interested in improving the assessment of cognition in Alzheimer’s patients, and devised CANTAB (Cambridge Neuropsychological Test Automated Battery), with Professor Trevor Robbins. We were keen that the test be easy to use, so we used what was then highly novel touch-screen technology. These tests were not language based, in order that the results were not confounded by either intelligence level or language proficiency. This of course meant that Cantab was also suitable for translational studies. With these features and aims in mind, the computerized cognitive neuropsychological test battery we developed for Alzheimer’s disease assessed processing speed, attention, memory and executive function.
The value of this approach is demonstrated in the utility of one task in particular: the Paired Associates Learning test (PAL). Cantab PAL measures episodic memory; the ability to learn, store, and retrieve information about past experiences. I often use the episodic memory example of parking your car in a multi-story car park while you go into work or go shopping and then coming back several hours later and having to remember where you parked your car so that you can retrieve it. Cantab PAL is a non-verbal assessment of memory, and so offers the advantage of being language and culture neutral, and translatable to research and healthcare settings globally. This task was used in research studies in patients, where it was found to be highly sensitive to Alzheimer’s disease, and could be used to detect clinically relevant memory problems in patients with questionable dementia, accurately identifying those who went on to decline.
PAL provides a rapid, noninvasive means of assessing memory problems in the elderly and change over time. For clinical trials, episodic memory tests such as PAL are likely to be the fastest and least expensive way to assess an individual’s risk for prodromal Alzheimer’s disease, helping to select or stratify patient populations that may be most suitable for intervention. The Cantab PAL test also provides an excellent outcome measure for symptomatic and neuroprotective treatments.
Recently PAL and other CANTAB tests have been made available in cloud based assessment tools for use in academic research specifically for use in dementia research. These new assessments include tests of visual episodic and short term memory, processing speed, sustained attention and executive function providing highly validated and precise measurements for research of Alzheimer's disease and mild cognitive impairment with the technology delivering incredibly high quality data.
The PAL episodic memory test has also been adapted and refined for use by primary care physicians, and the resulting tool, Cantab Mobile, has now been used to sensitively assess around 20,000 patients in the NHS, UK. Cantab Mobile allows clinicians in primary care to have a rapid decision making tool in regard to the cognitive functioning of their elderly patients. It has a very easy readout and only takes a few minutes. It can also be administered by a non-specialist.
To have the best outcome, early detection of Alzheimer’s disease is important. It allows treatments to be utilised at the earliest stage, so they can have the most benefit. Furthermore, it has been shown that early detection is cost effective. I am very pleased to see that since I started work in this area, many advances have been made. Governments and healthcare systems are becoming committed to early detection and treatment of dementia and stigma is much reduced within society. In addition, there are now excellent ways of detecting Alzheimer’s disease, such as the Cantab PAL, and that there are effective pharmacological treatments for the cognitive symptoms approved by international regulatory authorities. Currently, there are game-changing research studies on neuroprotective drugs, which aim to halt the underlying disease process. These substantial developments within a relatively short period of time provide great promise for successful ageing and good brain health in the future.