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What do we know about mild to moderate Alzheimer’s disease?

Posted on 30 June 2015 in Clinical Trials / Research

RESEARCH REVIEW

Alzheimer’s disease is the most common type of dementia, accounting for 60-80% of cases. It is characterized by progressive cognitive impairment, which impedes day-to-day function. In the early stages of Alzheimer’s disease, memory is most affected, but over time, other abilities 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 years. The economic cost of dementia is around 600 billion US dollars per year globally, including cost of health and social care, and loss of income resulting to patients and carers.

Pathology and functional impact of the disorder


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 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 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 accords closely with the progressive loss of everyday functioning observed in people with Alzheimer’s disease. In people with mild, early forms of Alzheimer’s disease there are typically problems performing well-circumscribed discrete tasks (e.g. remembering a newly introduced person’s name, or remembering where one put a valuable object). In moderate forms of the disorder, there can be more global difficulties with life tasks (e.g. forgetting one’s home address, or needing help from others choosing the appropriate clothing for the season).

Existing treatments and research and the need to improve


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 the 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.

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 diagnosis2. In another study, the prompt detection and treatment of Alzheimer’s disease was associated with estimated economic savings of around 10,000 USD per patient3.

The search for pharmacotherapies capable of stemming disease progression in Alzheimer’s disease, rather than providing only symptomatic relief, continues, and represents a key unmet need.

Accelerating development of Alzheimer’s treatments


Cantab Connect provides a rapid, reliable, and highly sensitive system for clinical trials and academic research. It identifies baseline impairment in mild-moderate Alzheimer’s disease with large effect sizes4, discriminates from the cognitive effects of depression5, and is highly sensitive to disease progression6. Further, the battery offers considerable advantage over traditional measures (ADAS-cog, MMSE) for predicting cognitive decline at an individual patient level7. Because of these properties, Cantab Connect Alzheimer’s maximises scope for sample enrichment, and for demonstrating disease modifying capability of interventions. The battery avoids floor and ceiling effects that are common with other testing batteries in the dementia field, by using carefully chosen ranged task-difficulties. Its simple touch-screen interface and large normative database make it ideally suited for use across the age span, including in elderly populations. Cantab Connect Alzheimer’s is clinically relevant: cognitive impairments on the battery correlate with everyday function and long-term outcomes in Alzheimer’s disease.

 

Cantab for Alzheimer’s in:

Academic research

Clinical development

 

References

1. Dementia: a public health priority. World Health Organisation and Alzheimer’s Disease International, 2012.

2. Barnett et al., BMC Neurol, 2014.

3. Getsios et al., Alz Dement, 2012.

4. Egerhazi et al., Prog Neuropsych Bio Psych, 2007

5. Swainson et al., Dement Ger Cogn Dis, 2001.

6. Chamberlain et al., J Alz Dis, 2011.

7. Blackwell et al., Dement Ger Cogn Dis, 2004.

 

Key research papers on Alzheimer’s disease:


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 May 7;14:101.

Chamberlain SR, Blackwell AD, Nathan PJ, Hammond G, Robbins TW, Hodges JR, Michael A, Semple JM, Bullmore ET, Sahakian BJ. Differential cognitive deterioration in dementia: a two year longitudinal study. J Alzheimers Dis. 2011;24(1):125-36.

Blackwell AD, Sahakian BJ, Vesey R, Semple JM, Robbins TW, Hodges JR. Detecting dementia: novel neuropsychological markers of preclinical Alzheimer's disease. Dement Geriatr Cogn Disord. 2004;17(1-2):42-8.

Swainson R, Hodges JR, Galton CJ, Semple J, Michael A, Dunn BD, Iddon JL, Robbins TW, Sahakian BJ. Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks. Dement Geriatr Cogn Disord. 2001 Jul-Aug;12(4):265-80.

View the abstracts in the Cantab Bibliography.