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Feature

Facts about Dementia

Posted on: 07 Feb 06

Summary

The symptoms of Alzheimer’s disease can be treated by a class of drugs known as cholinesterase inhibitors (ChEI’s), which increase the availability of acetylcholine in the brain by inhibiting the enzyme acetylcholinesterase (AChE).

Dementia is a neurodegenerative and devastating disease

Dementia is a degenerative disease of the brain that progressively destroys the neurons controlling memory, language and reasoning. It progresses at different rates in different people.

It is estimated that dementia currently affects nearly 18 million people worldwide (1). As the mean age of the population increases, these numbers are steadily increasing.

Forms of dementia and their estimated prevalence: 1

Alzheimer's disease (AD)

55%

Vascular dementia (VaD)

20%

Dementia with Lewy bodies (DLB) and dementia associated with Parkinson's disease

20%

Other dementias including fronto-temporal dementia including Pick's disease

5%

Alzheimer's Disease (AD) is the most common form of dementia

Alzheimer's disease is a progressive, degenerative disease that alters the brain, causing impaired memory, thinking and behavior. Abnormalities, such as protein patches and twisted threads that form between brain cells (amyloid plaques) or inside nerve cells (neurofibrillary tangles) are characteristics of Alzheimer's disease (2).

Brain activity involves the transmission of signals between nerve cells. This process relies on messenger substances called neurotransmitters working in healthy balance with the enzymes that break them down.

The Alzheimer's brain is associated with decreased transmission of the neurotransmitter acetylcholine, which is crucial for memory and thinking and behavior, due to an imbalance of enzyme activity. Acetylcholine is broken down by two enzymes called cholinesterases - specifically acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). (3) As Alzheimer's disease progresses, BuChE becomes increasingly active (4).

One in 10 individuals over the age of 65 years suffers from Alzheimer's disease. Alzheimer's disease is the third leading cause of death behind cardiovascular disease and cancer (5).

It is known that Alzheimer's patients who suffer rapid progression early in their disease have a poorer prognosis. (6)This rapid progression is responsible for additional distress to patients and their caregivers. (7) Patients who continue with a more rapid decline, enter severe stages of the disease earlier and eventually die earlier 4, (8). It is estimated that up to 45% of mild to moderate Alzheimer's disease patients experience rapid decline (9).

Parkinson's disease (PD) can be associated with dementia.

Besides motor symptoms, Parkinson's disease (PD) is frequently associated with cognitive impairment and dementia. It is estimated that two out of five people with Parkinson's disease develop dementia in the course of their disease (10).

The symptoms and neuro-pathological processes of dementia associated with Parkinson's disease are considered to be closely related to dementia with Lewy bodies (DLB) (11). In both conditions so-called Lewy bodies (spherical clusters of protein) develop in the brain, resulting in a disruption of the neuro-chemical balance of the brain and the loss of neurons (2), (12) .

Like Alzheimer's disease, many symptoms of dementia associated with PD and DLB, such as cognitive and behavioral problems observed in these patients, are thought to result from a cholinergic deficit. Patients with dementia associated with Parkinson's disease typically have problems with memory, concentration, activities of daily living, as well as depression, anxiety, apathy and hallucinations (12), (13).

The current treatments for Parkinson's disease target the management and improvement of motor symptoms but do not improve dementia symptoms. Dementia associated with Parkinson's disease can have a devastating effect on patients and their families as dementia symptoms are often more distressing than the motor symptoms of Parkinson's disease (15) .

Dementia has a profound impact on patients and their families

Memory loss is an integral part of ageing, however the consequences of dementia are more severe. Differences between normal ageing and signs of dementia include:

Normal Ageing

Signs of Dementia

Periodic forgetfulness

Increasing problems with short-term memory that interfere with daily functioning

Forgetting where car keys were placed.

Forgetting what car keys are used for

Forgetting a friend's birthday

Difficulty recognizing friends and family

Occasionally misplacing items

Putting things in strange places (for example, placing an iron in the refrigerator)

Dementia affects the neurons responsible for memory. Its onset is insidious, but its progress is devastating as patients become increasingly helpless and dependent on their families or caregivers. Having to watch their loved ones deteriorate has a profound effect on caregivers and many develop depression as a result (14).

Patients with dementia can experience

• memory loss

• loss of intellectual abilities severe enough to interfere with routine and social activities

• confusion

• language problems (trouble finding words)

• poor or decreased judgment

• disorientation in place and time

• aggression

• behavioral and personality changes, such as inappropriate behavior

In addition, patients with dementia associated with Parkinson's disease and DLB may also experience apathy, poor concentration and are more likely to encounter hallucinations (15).

Dementia results in increased economic and social burden

Behavioral and psychological symptoms of dementia contribute considerably to social and economic burdens. Symptoms are accompanied by a decline in functioning and a marked reduction in the quality of life for patients (16) and place considerable stress on caregivers (17). The ability to treat these symptoms have enormous potential for improving patients' and caregivers' quality of life and prolonging the time patients are able to stay in the community, thereby also reducing the costs associated with institutionalization (18), (19), (20).

The potential health risks to caregivers and the increased time spent out of the workplace contribute to the economic burden associated with AD (21), (22). Moreover, the presence of behavioral symptoms is often the single largest factor in the decision to institutionalize patients with AD (23), (24), (25), resulting in considerable costs of intensive nursing care.

Dementia is associated with ageing

The risk of developing dementia increases with age. Ninety to ninety-five percent of all Alzheimer's cases occur in people age 65 and older. 8 Rarer is the early onset of Alzheimer's (in people under 65) and familial Alzheimer's that is a hereditary condition. Other risk factors include:

• a family history of dementia

• a history of head trauma

• Down's syndrome

• socio-economic factors such as low education

• ethnicity (Blacks and Hispanics are more likely to develop it than Caucasians) (3)

Research also indicates that over three quarters of patients with Parkinson's disease develop dementia in the course of their illness. (2)

Dementia affects a growing patient population across the globe

Statistics show that dementia rises exponentially with age. As life expectancy increases and more people live to the age of 80+, the number of dementia patients will increase:

• Currently nearly 18 million people worldwide suffer from dementia, which is comparable to the number of people living in Australia.

• By 2025 their number is expected to rise to 34 million (1) , which will be more than the current number of inhabitants of Canada.

Dementia cannot be cured, but it can be treated

While Alzheimer's disease and related dementias cannot be cured at the moment, the progress of symptoms can be delayed. The earlier it is diagnosed and treated, the better for the patient and his/her family.

Although there is currently no conclusive diagnostic instrument apart from autopsy, doctors can correctly diagnose Alzheimer's at an accuracy rate of 90 percent (26). Instruments used include:

• detailed medical history and complete physical examination

• neurological examination to measure memory and language functions

• psychiatric assessment

• laboratory tests to exclude other underlying causes such as tumors or strokes.

The exact cause of dementia is still uncertain, but research indicates that memory loss may occur as a result of decreased transmission of signals between nerve cells in the brain that rely on the neurotransmitter acetylcholine.

Acetylcholine is the neurotransmitter that is crucial for memory, thinking and behavior. In the brains of patients with AD, acetylcholine is broken down by enzymes called cholinesterases.

The symptoms of Alzheimer's disease can be treated by a class of drugs known as cholinesterase inhibitors (ChEI's), which increase the availability of acetylcholine in the brain by inhibiting the enzyme acetylcholinesterase (AChE).

There is one treatment, Exelon ® (rivastigmine tartrate), with a dual mode of action that also blocks butyrylcholinesterase (BuChE), the second enzyme responsible for reducing the available levels of acetylcholine in the brain. (27) The inhibition of both enzymes – AChE and BuChE - increases the availability of acetylcholine in the brain and thus may help explain the drug's long-term efficacy. (28)

Exelon can maintain both memory and thinking, help with behavioral problems and affect how patients cope with the activities of daily living. It may help them communicate better, interact socially, participate in hobbies and eat and dress independently (29), (30).

Exelon is widely used in the treatment of mild to moderate Alzheimer's disease and is the first treatment that has been shown to also have a significant effect in treating dementia associated with Parkinson's disease (31). The EXPRESS study, published in the New England Journal of Medicine , shows that Exelon can improve the symptoms of dementia associated with Parkinson's disease, such as loss of memory, concentration and behavioral problems. (Please also refer to “EXPRESS Study Fact Sheet”).

References

1. Alzheimer's Society Policy Position Paper, January 2004. www.alzheimers.org.uk/News_and_Campaigns/News_and /Policy/demography.htm May 2004.

2. 2000 Progress Report on Alzheimer's Disease. Taking the Next Steps' The National Institute of Aging (NIA) and the National Institutes of Health (NIH), p6.

3. Giacobini E. Inhibition of acetyl-and butyrylcholinesterase in the cerebrospinal fluid of patients with Alzheimer's Disease by rivastigmine: correlation of cognitive benefit. J Neural Trans 2002; 109:1053-1065

4. Perry EK, Perry RH, Blessed G, et al. Changes in brain cholinesterases in senile dementia of the Alzheimer type. Neuropath Applied Neurobiol 1978;4:273–7.

5. Evans DA, Funkenstein HH; Albert MS et al. Prevalence of Alzheimer's disease in a community population of older persons: Higher than previously reported. JAMA 1989;262(18): 2552-2556.

6. Doody et al. A method for estimating progression rates in Alzheimer's disease. Arch Neurol 2001; 58: 449-454.

7. Excites Market Research 2002. Data on file. Novartis Pharma AG.

8. Hui et al. Rate of cognitive decline and mortality in Alzheimer's Disease. Neurology 2003; 61:1356-1361.

9. Farlow MR et al. Response of patients with Alzheimer's disease to rivastigmine treatment is predicted by the rate of disease progression. Arch Neurol 2001; 58:417-422.

10. Emre M. Dementia associated with Parkinson's disease. Lancet Neurology 2003; 2: 229-37.

11. McKeith IG and Mosimann UP. ‘Dementia with Lewy bodies and Parkinson's disease.' Parkinsonism & Related Disorders 10 (2004) S15-S18.

12. Huber SJ, Paulson GW, Shuttleworth EC. Relationship of motor symptoms, intellectual impairment, and depression in Parkinson's disease. J Neurol Neurosurg Psychiatry 1999;14:866-74.

13. Emre M. Dementia associated with Parkinson's disease. Lancet Neurology 2003; 2: 229-37.

14. Aarsland D et al. Mental symptoms in Parkinson's disease are important contributors to caregiver distress. Int J Geriatr Psychiatry 1999; 14:886-74.

15. Korczyn A. ‘Dementia in Parkinson's disease' J Neurol (2001) Suppl 3, III1-III/4

16. Whitehouse PJ, Orgogozo JM, Becker R. Quality of life assessment in dementia drug development. Alzheimer Dis Assoc Disord 1997; 11 (Suppl3): 56-60.

17. Dura JR, Stukenberg KW, Kiecolt-Glaser JK. Anxiety and depressive disorders in adult children caring for demented parents. Psychol Aging 1991; 6: 467-73.

18. Fraser M, Snyder E. The economic benefits of delaying progression in Alzheimer's disease using cholinesterase inhibitors. Neurology 2000; 8: 72-93.

19. Fenn P, Gray A. Estimating long term cost savings from treatment of Alzheimer's disease. Pharmacoeconomics 1999; 16: 165-74.

20. Hauber AB, Gnasasakthy A, Snyder EH, et al. Potential savings in the cost of caring for Alzheimer's disease: treatment with rivastigmine. Pharmacoeconomics 2000; 17: 351-60.

21. Wimo A, Ljunggren g, Winblad B, et al. Costs of dementia and dementia care; a review. Int J Geriatr Psychiatry 1997: 12: 841-56.

22. Hux MJ, O'Brien BJ, Iskedjian M, et al. Relation between severity of Alzheimer's disease and costs of caring. CMAJ 1998; 159: 457-65.

23. Cummings JL. Theories behind existing scales for rating behaviour in dementia. Int Psychogeriatr 1996; 8: 293-300.

24. Steele C, Rovner B, Chase GA, Barnes HJ, et al. Psychiatric symptoms and nursing home placement of patients with Alzheimer's disease. Am J Psychiatry 1990; 147: 1049-51.

25. O'Donnell BF, Drachmann DA, Barnes JH, et al. Incontinence and troublesome behaviours predict institutionalization in dementia. J Geriatr Psychiatry Neurol 1992: 5; 45-52.

26. American Family Physician. Diagnosis and Management of Dementia. Monograph 2, 2001, p 8.

27. Ballard CG. Advances in the Treatment of Alzheimer's Disease: Benefits of Dual Cholinesterase Inhibition. European Neurology 2002; 2002;47(1):64-70.

28. Gauthier S. Brain Aging 2002:2:9-22.

29. Corey-Bloom J, Anand R, Veach J. A randomized trial evaluating the efficacy and safety of ENA713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Geriatr Psychopharmacol 1998;1:55-65.

30. Rösler M, Anand R, Cicin-Sain A et al. Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomized controlled trial. Br Med J 1999;318:633-40.

31.Emre M et al. Rivastigmine for the dementia associated with Parkinson's Disease. N Engl J Med 2004;351:29-38.

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Stephen Cull

Last updated on: 27/08/2010 11:40:18

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