Alzheimer’s disease (AD) is a terminal neurodegenerative condition that causes cognitive decline and dementia in sufferers. In the UK, around 820,000 people have dementia, with AD being responsible for around 60 % of all cases. Like other forms of dementia, AD is an extremely debilitating condition. Sufferers find it increasingly difficult to perform the every-day tasks necessary for independent living, and eventually require help with the simplest of tasks. As a result, most dementia sufferers become substantial users of health and social care services. There are two major types of AD, late-onset, and early-onset. Late-onset AD can affect people after age 65, and is the most common form of the disorder being responsible for around 90% of all cases. Early-onset AD can affect people before their 65th decade of life, and is rare, accounting for less than 10% of cases overall. Whilst in most of these cases AD is not caused by mutations (i.e. mistakes) in particular genes (i.e. the instructions for building proteins), certain forms (or variants) of some genes, have been linked to an increased risk of developing the disorder. However, in about 1% of cases AD is classed as “Familial”, being inherited due to genetic mutations associated with the overproduction of the amyloid precursor protein, or its biochemical processing into amyloid-beta peptides. Familial AD can affect people in their 40th decade of life.
As a neuroscientist my interest in brain research stems from my childhood experience of watching my grandfather succumb to AD. My grandfather was a much loved person who had a friendly vitality for life. I remember standing at his graveside, and thinking as the coffin was lowered into its final resting place, that one day I would like to understand enough about the brain to maybe help others avoid this devastating illness. To this end I have conducted research at Cardiff University, which has examined the possible therapeutic effects of anti-inflammatory compounds in AD.
The pathology of AD has been studied intensely in the last 20 years or so in both humans and with the aid of animal models related to the condition. Whilst these studies have provided valuable information with respect to our understanding of AD, many important questions remain unanswered. AD is an extremely complex condition, where genes, the environment and various life-style choices, all interact with each other to produce the dementia syndrome. Population-based neuropathology studies have revealed that AD-type brain pathology forms a continuum in the ageing population, with considerable overlap in the burdens of pathology seen in demented verses non-demented individuals. Establishing common pathological thresholds for cognitive impairment and dementia based on these components is a work in progress. Like most forms of dementia, AD is a progressive condition, with symptoms worsening over time. This is largely thought to reflect pathological changes taking place in the brain, which affect its chemistry, structure, and function. These changes are evident in the parts of the brain dealing with memory, especially structures in the medial temporal lobe system (MTLs). This part of the brain is vital for declarative memory - the conscious recall of facts (i.e. semantic memory) and information relating to autobiographical life events (i.e. episodic memory), as well as spatial navigation, which we use to find our way around a familiar environment. The MTLs is also necessary for recognising objects and their spatial locations (i.e. visuospatial memory). Pathological changes in this and nearby parts of the brain likely explain why it is that people in the early-stages of AD often experience memory problems such as forgetting recent conversations or appointments, getting lost, and misplacing personal objects of interest. However, AD is not just about being forgetful, it is about staring at your car keys wondering what they are for, or perhaps opening your fridge and finding your car keys or slippers inside.
The MTLs and nearby brain regions are also involved in communication, particularly language. People with early-stage AD will therefore often experience difficulties communicating. This aspect of AD is poignantly conveyed in the film “Poetry”, where the lead character is suffering from early stage AD whilst learning to be a poet. Whilst the character is able to understand what other people are saying, and can respond, they are sometimes slow in verbal expression due to trouble finding words. It is also common for people with AD to repeat comments or phrases, or have difficulty with verbal expression because they cannot maintain a train of thought. What is interesting about the poetry written by people with AD is that it often appears Zen-like, focused on the experience of the here and now, with a simpler sentence construction that is often minimalist in nature. These poems are powerful because of these features. Individuals with severe AD can still recall lines of poetry they may have learnt as children, and encouraging the recital of these can help improve the quality of patient’s lives by encouraging interaction. Over time various cognitive and behavioural circuits in the brain continue to degrade. Eventually sufferers are robbed of the very thoughts and memories which make all of us unique human beings. To paraphrase Rutger Hauer at the end of the film Blade Runner, [eventually], “All those moments, will be lost in time, like tears in the rain”. And yet, many individuals can be encouraged to learn new things, as implicit memory for skills (which does not require conscious recall), is still largely intact even in severe AD. Thus, encouraging the individual to paint or draw, can improve their social interaction and thus quality of life. It is also the case that skills learnt when a person was younger, such as playing the piano, can still be elicited well into the time course of the illness. Such activities can bring back (even if fleetingly) fragments of memory, and improve the persons quality of life. Unfortunately however, in many nursing homes, staff members, who are often under-resourced, and under-paid, do not have the time or motivation to encourage such activities, often reverting to a chemical cosh to keep patients with AD quiet. This is inhumane, and needs to change.
It is extremely likely that what we currently understand as early-onset and late-onset AD may turn out to be a generalisation for perhaps several overlapping sub-types of the illness (each like variations on a theme). Most pharmaceutical companies aim to produce blockbuster drugs, which are effective across a range of disease conditions (or disease sub-types). This is likely not an optimal strategy for AD. Providing we can accurately identify sub-types of AD, what may prove more effective is to conduct clinical trials for drug therapies on specific sub-types of the illness. It’s time we adopted a more holistic approach to treating AD, as without embracing its true complexity we are unlikely to succeed in treating the condition.
John Anderson - School of Biosciences, Cardiff University