Geriatric Nursing
Volume 24, Issue 1 , Pages 64-65, January 2003

Steps taken toward improving dementia treatment during 2002

CAROL A. MILLER, RNC, MSN, is a gerontological nurse specialist with Care and Counseling, Miller/Wetzler Associates, Cleveland, Ohio. She invites questions for this column at cmdrugconsult@aol.com

Article Outline

 

In keeping with the theme of this issue of Geriatric Nursing , this column presents an overview of research findings from 2002 related to drugs that have been approved or are in development for the treatment or prevention of dementia. The sidebar summarizes research highlights, which are categorized according to their impact on progress toward the goal of advancing drug therapies for dementia.

Although 2002 was the first year since 1999 in which the Food and Drug Administration did not approve any new drugs for dementia, new and valuable information about cholinesterase inhibitors emerged from studies. Since the 1990s, clinical trials of cholinesterase inhibitors, the only drugs approved for treatment of Alzheimer disease (AD), have shown moderate improvement in cognitive, behavioral, and functional deficits associated with mild to moderate AD. Studies published during 2002 expanded our knowledge about differing and longer-term effects of three of the four approved drugs: tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl). No studies of tacrine, the first cholinesterase inhibitor, were published in 2002, and the more recently developed drugs have largely replaced it. Current studies are addressing the use of cholinesterase inhibitors in types of dementia other than AD (eg, vascular and Lewy body).

Probably the most exciting area of research on drugs for dementia is the potential role of statins (HMGCoA reductase inhibitors), drugs already widely used for hyperlipidemia. Epidemiological studies indicate that statins may be effective in preventing and treating dementia, and additional studies are in progress to explore the potential of these drugs. Studies also are underway to explore the relationship between statin drugs and pathological processes that cause dementia. One theory is that statins decrease beta-amyloid by decreasing the cholesterol burden and improving endothelial function and microvascular flow.1 However, another study2 concluded that clinical doses of statins do not significantly affect beta-amyloid secretion, but other effects of these drugs may be responsible for protecting against dementia.

Cholinesterase Inhibitors

•Rivastigmine is less likely than donepezil or galantamine to interact with other drugs (particularly those that are metabolized in the liver) and therefore may be safer and better tolerated in people with concomitant illnesses.1

•Rivastigmine is effective across the range of dementia severity (from mild to severe) for the treatment of behavioral, psychological, and cognitive symptoms in several types of dementia.2

•Patients with Lewy body dementia showed improvements in cognition during a 20-week study of rivastigmine.3

•Rivastigmine may be effective for at least 2 years in the treatment of dementia and may slow the progression of AD.4

•Galantamine is effective for treating cognitive and behavioral symptoms in both AD and vascular dementia. In mild stages, the improvement is primarily cognitive; in later stages, the improvement is primarily behavioral.5

•Cholinesterase inhibitors may be useful in treatment of vascular dementia.6

Other Drug Therapies

•Long-term use of nonsteroidal anti-inflammatory drugs may decrease the risk of AD if the use of these drugs occurs well before the onset of dementia.7

•A retrospective longitudinal study indicated that statins are effective in decreasing the prevalence of dementia and arresting the progress of cognitive impairment.8

•Nimodipine (Nimotop), a calcium channel blocker used since 1988 for cardiovascular disease, is prescribed for dementia in European countries and may be of some benefit.9

•A multicenter, randomized, double-blind clinical trial of the neurotrophic agent, cerebrolysin (Cere), found significant cognitive improvement in the AD treatment group after 2 months.10

•A multicenter clinical trial of memantine for the treatment of mild to moderate vascular dementia showed improved cognition and no deterioration in behavior and global functioning in the treatment group during a 28-week period.11

•A study of estrogen therapy in patients with aggressive behavioral disturbances found significantly greater improvements in dementia-related behaviors.12

•A 4-month study found that melatonin (6 mg daily) improved sleep and suppressed sundowning (ie, the onset of agitated behaviors in the late afternoon or early evening) in people with AD.13

Hope on the Horizon

•Clinical trials of statins for AD treatment

•Stem-cell therapies

•Development of vaccination with beta-amyloid fragments

•Development of β- and γ-secretase inhibitors

For several years, researchers have been addressing questions about the inflammatory process as a causative factor in dementia, and pharmaceutical companies have been particularly interested in the potential role of anti-inflammatory drugs for preventing or treating dementia. Studies published during 2002 do not support the use of these drugs for treatment, but they indicate that there may be a role for anti-inflammatory drugs in dementia prevention. In addition, researchers continued to focus on the development of new types of drugs for dementia and safe and effective drugs to manage dementia-related behaviors.

This column would be remiss if it did not mention the major recent disappointment associated with the cessation of clinical trials of the human beta-amyloid vaccine for AD because some participants developed meningoencephalitis. Despite this step backward and a few other disappointments, 2002 heralded much new information leading to developments in both prevention and treatment of dementia, and hope still hovers on the horizon.

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References 

  1. Drachman DA. The treatment of Alzheimer's disease: where have we been, and where are we going?. Am J Alzheimers Dis Other Demen. 2002;17(3):133–134
  2. Fassbender K, Stroick M, Bertsch T, Ragoschke S, Kuehl S, Walter S, et al.  Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide. Neurology. 2002;59:1257–1258
  3. Inglis F. The tolerability and safety of cholinesterase inhibitors in the treatment of dementia. Int J Clin Pract Suppl. 2002;127:45–63
  4. Rosler M. The efficacy of cholinesterase inhibitors in treating the behavioral symptoms of dementia. Int J Clin Pract Suppl. 2002;127:20–36
  5. Wesnes KA. Effects of rivastigmine on cognitive function in dementia with Lewy bodies. Dement Geriatr Cogn Disord. 2002;13(3):183–192
  6. Farlow MR. Do cholinesterase inhibitors slow progression of Alzheimer's disease?. Int J Clin Pract Suppl. 2002;127:37–44
  7. Erkinjuntii T. Treatment options: the latest evidence with galantamine (Reminyl). Neurol Sci. 2002;203–204(C) 125-30
  8. Roman GC. Vascular dementia revisited: diagnosis, pathogenesis, treatment, and prevention. Med Clin North Am. 2002;86:477–499
  9. Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JCS, et al.  Reduced incidence of AD with NSAID but not H2 receptor antagonists. Neurology. 2002;59:880–886
  10. Hajjar I, Schumpert J, Dirth V, Hirth V, Wieland D, Elazer GP, et al.  The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Ger Med Sci. 2002;57A:M414–M418
  11. Lopez-Arrieta JM. Nimodipine for primary degenerative, mixed and vascular dementia. Cochrane Database Systems Review. 2002;3:CD000147
  12. Panisset M. Cerebrolysin in Alzheimer's disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. J Neural Transm. 2002;109:1089–1104
  13. Orgogozo JM. Efficacy and safety of memantine in patients with mild to moderate vascular dementia. Stroke. 2002;33:1834–1839
  14. Kyomen HH. Estrogen therapy and noncognitive psychiatric signs and symptoms in elderly patients with dementia. Am J Psychiatry. 2002;169:1225–1227
  15. Cardinali DP. The use of melatonin in Alzheimer's disease. Neuroendocrinol Lett. 2002;23(Suppl 1):20–23

PII: S0197-4572(03)50002-7

doi:10.1067/mgn.2003.1

Geriatric Nursing
Volume 24, Issue 1 , Pages 64-65, January 2003

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