Alzheimer’s disease (AD) is emerging as one of the most important global public health issues to face modern humanity. It is the most common cause of dementia, accounting for over 70% of cases, and is characterised by cognitive decline, abnormal β-amyloid protein plaque deposition in the brain and neurotoxicity with loss of the brain tissue. The incidence increases significantly with age, with 1 in 3 over the age of 85 suffering from the disease. With the aging population and success of medical interventions in many other disease areas, the prevalence of AD is rapidly increasing. Data from the 2015 World Alzheimer’s Report estimates there are 47 million people globally affected by AD, with the number set to double every 20 years. The burden of the disease is global, with nearly 70% of the increase expected to be in middle and low income countries.
In Australia, more than 342,800 people are living with dementia, with the number expected to be almost 900,000 by 2050. The number of people with AD in the United Kingdom (UK) has increased since the late 1990s and is a major cause of morbidity and mortality. Of the 5.3 million Americans with AD, an estimated 5.1 million are aged 65 years and older, and approximately 200,000 are under the age of 65. By 2025, the number of people aged 65 and older with AD is estimated to reach 7.1 million – a 40% increase from the 5.1 million aged 65 and older affected in 2015. By 2050, this number could triple to a projected 13.8 million, barring the development of medical breakthroughs to prevent or cure the disease.
The cost of treating AD is approaching one trillion dollars – if dementia care was a country it would be the 18th largest economy. AD is one of the leading causes of death in the developed world, and in Australia is second only to ischemic heart disease. Compounding this societal burden however, is the relatively limited benefit provided by the currently available treatment options for Alzheimer’s disease. None of the main four registered drugs (donepezil, rivastigmine, galantamine and memantine, which are available in a number of different formulations), provide much more than short-term symptomatic benefit, and significantly, none are disease‑modifying. The Alzheimer’s disease community desperately needs new alternative treatment options, and ideally, drugs with a disease‑modifying potential.
Alzheimer’s disease is now understood to be a disease that develops years before it becomes symptomatic, with the development of dementia. It is likely that brain pathology begins to develop up to 15 years before the appearance of mild cognitive impairment or clinical dementia. The discovery and development of mechanisms for earlier diagnosis and treatment is therefore vital to be able to significantly impact the burden of the disease on modern society.
While no single clear cause for the development of Alzheimer’s disease has been reported, there is strong evidence to support an association between excess cortisol – the “stress hormone”, and the development of Alzheimer’s disease (see data from Popp et al). Excess cortisol has been shown to cause cognitive decline, and to lead to β-amyloid plaque deposition and neurotoxicity in the brain, and to the loss of brain tissue. All these are hallmarks of Alzheimer’s disease.