Alzheimer’s disease

Alzheimer’s disease is the most common type of dementia, accounting for 60-80% of cases. It is characterised by progressive cognitive impairment, which impedes day-to-day function.

In early (prodromal) stages of Alzheimer’s disease, there is typically subtle loss of memory abilities, but everyday function and quality of life is relatively intact. As the disease progresses memory is most affected, but over time, other abilities can deteriorate including planning, language, and learning capacities.

Dementia knows no boundaries in terms of gender, culture, or socioeconomic class. Thirty-five million individuals are affected worldwide, with a new case of dementia developing every four seconds, and the prevalence expected to double every 20 years¹.

The economic cost of dementia is around 600 billion US dollars per year globally, this includes the cost of health and social care and loss of income resulting to patients and carers.
 

Pathology and functional impact of Alzheimer’s disease

Classical understanding of the underlying brain pathology in Alzheimer’s disease emphasises the laying down of beta-amyloid plaques outside of brain cells, coupled with the accumulation of tau proteins within brain cells. There is a concomitant loss of the neurotransmitter acetylcholine in the cortex.

These pathological processes begin long before the symptoms become evident, and before a formal diagnosis is possible using usual methods.  The diagnosis of Alzheimer’s disease is made on the basis of a detailed clinical assessment and biomarkers (e.g. neuroimaging). 

Early in this chain of pathogenesis of Alzheimer’s disease, there is typically selective impairment in episodic memory. Later on, cognitive deficits across other domains commonly develop, especially for other memory processes (semantic and working memory), executive planning, and attention. This progression and spread of cognitive dysfunction links closely with the progressive loss of everyday functioning observed in people with Alzheimer’s disease.

In people with prodromal Alzheimer’s disease, or Mild Cognitive Impairment (MCI), every-day functioning is either intact, or there are relatively subtle problems with complicated tasks. For example, an individual with MCI may need more time than before to deal with household bills or to prepare a shopping list; or make occasional errors in these chores that are out of character.

In moderate forms of Alzheimer’s disease, there are more global difficulties with life tasks (e.g. forgetting one’s home address, or needing help from others in choosing appropriate clothing for the season).
 

Research and development in Alzheimer’s disease

Comprehensive treatment of Alzheimer’s disease should involve a multidisciplinary approach, including consideration of medications. Currently available, licenced drug treatments for Alzheimer’s disease do not significantly slow the underlying progression of disease, but rather provide symptomatic relief to maximise comfort, dignity, and independence.

Cholinesterase inhibitors (e.g. donepezil, rivastigmine) represent first-line drug therapy for mild-moderate Alzheimer’s disease. These medications inhibit the brain’s breakdown of the neurotransmitter acetylcholine, helping to preserve memory and other cognitive functions.

People identified with possible prodromal Alzheimer’s disease, or MCI, are at increased risk of developing dementia. There are currently no licensed medications specifically for MCI. Rather, its detection allows for healthcare providers to monitor people more closely over time, but also allows individuals and their healthcare teams to work on risk reduction strategies.

Through the lifespan, at least half of the risk for dementia is potentially modifiable; for example, through improved diet, exercise, and avoiding smoking². Early detection also allows individuals to plan ahead and think about ‘what if’ their cognitive problems were to become more problematic in the future. 

Early detection of people at risk of developing Alzheimer’s disease leads to closer monitoring, enabling quicker intervention if the full disease develops.

The early detection of Alzheimer’s Disease, coupled with prompt intervention, is important for improving patient outcomes (and support for carers), but also from an economic perspective.  In a statistical modelling study, the maximum benefit from symptomatic treatment of Alzheimer’s disease (in terms of economic savings and gain in quality adjusted life years) was achieved when treatment was given as early as possible, e.g. eight years before standard diagnosis³. In another study, the prompt detection and treatment of disease was associated with estimated economic savings of around 10,000 USD per patient².

Treatment of Alzheimer’s disease includes consideration of specific medications. Currently available, licensed drug treatments for Alzheimer’s Disease do not significantly slow the underlying progression of disease, but rather provide symptomatic relief to maximise comfort, dignity, and independence.

The search for pharmacotherapies capable of averting disease progression in prodromal dementia, rather than providing symptomatic relief later after disease develops, continues and represents a key unmet need.
 

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You might also be interested in…

Albert M.S., et al (2011). The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement.

Barnett J.H., et al (2014). Early intervention in Alzheimer's disease: a health economic study of the effects of diagnostic timing. BMC Neurol.

Chamberlain S.R., et al (2011). Differential cognitive deterioration in dementia: a two year longitudinal study. J Alzheimers Dis.

Blackwell A.D., et al (2004). Detecting dementia: novel neuropsychological markers of preclinical Alzheimer's disease. Dement Geriatr Cogn Disord.

Swainson R., et al (2001). Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks. Dement Geriatr Cogn Disord.

Fowler K.S., et al (2002). Paired associate performance in the early detection of DAT. J Int Neuropsychol Soc.
 

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1. _{Wortmann M. (2012). Dementia: a global health priority - highlights from an ADI and World Health Organization report. Alzheimers Res. Ther. 4:40 10.1186/alzrt143}
2. _{Barnett JH, Lewis L, Blackwell AD, Taylor M. Early intervention in Alzheimer’s disease: a health economic study of the effects of diagnostic timing. BMC Neurol. 2014;14(101):101.}
3. _{Getsios D, Blume S, Ishak KJ, Maclaine G, Hernández L. An economic evaluation of early assessment for Alzheimer’s disease in the United Kingdom. Alzheimers Dement. 2012;8:22–30. doi: 10.1016/j.jalz.2010.07.001.}