Drug Use In The Elderly: Risk or Protection?

Christel Cornelius


Curr Opin Psychiatry. 2004;17(6) 

In This Article

Treatment of Dementia

To date, various agents for symptomatic treatment of dementia can be offered to patients. For primary and secondary prevention of dementia, some promising results have been presented. Future therapy will hopefully cure or delay the disease progression.

The AChEIs are prescribed for symptomatic treatment of mild to moderate Alzheimer's disease. Donepezil, rivastigmine, and galantamine had similar treatment effects at 6 months on global and cognitive rating scales.[28**] Two metaanalyses concluded that AChEIs show modest but significant therapeutic effects on Alzheimer's disease,[29**] and modest beneficial impact on neuropsychiatric symptoms and functional impairment in Alzheimer's disease.[30**] New data have suggested that AChEIs can be of use in vascular dementia[31**] and in more advanced stages of dementia as well.[32**] Furthermore, beneficial effects have been found with a combination therapy of memantine and donepezil in moderate to severe Alzheimer's disease.[33*] Memantine is a safe drug and may be useful for patients with Alzheimer's disease, vascular dementia, and mixed dementia, according to a Cochrane review.[34]

Atypical antipsychotics, serotonergic agents, and anticonvulsants may be well tolerated and useful in the treatment of behavioural and psychological symptoms in dementia, such as sleeping disorder, anxiety, depressed mood, agitation, and psychotic symptoms.[27**,32**]

In primary and secondary prevention of dementia, treatment of hypertension and control of other vascular risk factors, such as hypercholesterolemia, and cardio- and cerebrovascular diseases may decrease the incidence of dementia.[35*] Antihypertensive drug use showed an inverse association with the incidence of Alzheimer's disease in a study of the Kungsholmen Project.[36*] Population-based studies have not been able to show a protective effect of calcium channel blockers,[37] and no new studies have been published since 2003 on this topic. Whether antihypertensive treatment with calcium channel blockers can protect against dementia, as found in the Syst-Eur trial,[11] needs to be studied further. In two studies[38**,39*] active antihypertensive treatment with perindopril and candesartan, respectively, reduced the risk of stroke, and probably due to this effect, also reduced the risk of dementia.[38**] The control of blood pressure may be more important than the use of a specific antihypertensive drug.

Observational studies of dementia have shown promising results concerning a protective effect of statins, but so far, randomized trials have not been able to confirm these results.[40**]

In both experimental and epidemiological studies, estrogen has been found to have neuroprotective effects. The Women's Health Initiative Memory Study investigated women 65 years and older, treated with estrogen and progestin (n=4532), or estrogen alone for women with prior hysterectomy (n=2947).[41**] The combined therapy increased the risk of dementia, whereas the estrogen therapy neither increased nor decreased the risk.

The effect of nonsteroidal antiinflammatory drugs (NSAIDs) on the risk of Alzheimer's disease was systematically reviewed in a metaanalysis by Etminam and Samii.[42**] The results supported a protective effect against Alzheimer's disease among persons who used NSAIDs for at least 2 years. A possible protective effect was also found in the Kungsholmen Project, among long-term users of NSAIDs.[43*] Since 2001 a randomized trial has been investigating the effect of celecoxib and naproxen on the incidence of Alzheimer's disease in a population with increased risk of dementia,[44] and will probably give an answer to whether those NSAIDs can protect against Alzheimer's disease.

Future drugs will hopefully target the pathological events of dementia, and hence be able to slow down or interrupt the progress of, or even prevent, the disease. For Alzheimer's disease, the first human trials with immunotherapy[45] aiming at reducing the β-amyloid in the brain, had to be stopped because of serious adverse events. There is still hope of a vaccine against Alzheimer's disease, however, with a modified substance without a neuroinflammatory response causing meningoencephalitis.[28**] Other agents of interest in the search for a cure for Alzheimer's disease include inhibitors of γ- and β-secretase, amyloid antiaggregants therapy, and metal chelators.[28**,46**].


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