Irritability has many causes, but often reflects disease involvement by the frontal lobes (areas in the front part of the brain). We know that because people who have localized damage to their frontal lobes (say from a car accident, bullet, tumor Tumor
An abnormal mass of tissue that is the result of excessive cell division. They are not useful to the body and can be benign (non-cancerous) or malignant (cancerous). or blood vessel problem) characteristically lose interest in the people and things around them. (Notice that we are not saying that initiative 'rests' in the frontal lobes, or 'takes place' there. It is more realistic to think about initiative coming about as a result of a very complex circuit, which critically requires the frontal lobes, but which also requires activation of other parts of the brain.)

In the past, frontal lobe impairment was classically seen as a late sign Sign
In medicine a sign is what a physician finds by examining a patient. For example, a patient with the symptom of pain might have signs of a fast heart rate, a pale face, a clammy touch and tenderness. of Alzheimer's disease Alzheimer's disease
A neurological disease that affects memory and behaviour. It is characterized by beta-amyloid plaques and neurofibrillary tangles in the brain. There is no known cause but genetics and lifestyle are thought to play a role., but thinking about this has changed in two ways. Now that there is better testing of the frontal lobes, we see that this area of the brain is involved much earlier. Also, brain imaging studies suggest that early on, the brain is able to compensate for damage in the frontal lobes. However, the ability to compensate becomes less as the disease progresses. This is an important insight, because it suggests that strategies to treat Alzheimer's disease should not just focus on countering the disease process, but should also enhance the repair process.

This issue is explored in considerable detail in the chapter on 'Executive Function' by Sarah Voss and Roger Bullock, in the book Trial Designs and Outcomes in Dementia Therapeutic Research, published in London by Taylor & Francis, 2005, and edited Kenneth Rockwood and Serge Gauthier.

Irritability is often accompanied by anxiety and depression Depression
A disorder where a person experiences a constant state of sadness and low mood which interferes with their daily activity.. As such, people with Alzheimer's disease sometimes can respond to specific treatment for depression, especially with drugs that increase the level of serotonin. Although many physicians will attest to this, demonstrating the existence of a syndrome of "Dementia Associated Depression" has been difficult, and so too has been the effect of treating it.

This issue is explored in more detail in the chapter on 'Psychotropic agents in Alzheimer disease by David M. Blass, and Peter V. Rabins in the book Trial Designs and Outcomes in Dementia Therapeutic Research, published in London by Taylor & Francis, 2005, and edited Kenneth Rockwood and Serge Gauthier.