Drugs for Prevention and Disease Modification

AD is an insidious disease; sometime years go by before symptoms become noticeable. Disease prevention, therefore may be beneficial, and may decrease the prevalence of AD. Studies assessing prevention are underway.

§  NSAIDS: One such prevention study is evaluating the use of NSAIDS (non steroidal anti-inflammatory drugs) on AD. Preliminary results are promising, however AD researchers are reluctant to recommend NSAIDS given the toxicities (gastrointestinal ulcers, renal toxicity, hypertension) associated with taking these medicines. Researched are waiting for results from large RCTs in order to weigh the risks versus benefits of NSAID therapy before making any recommendations.30

§  Antioxidants. Pathological data indicates that oxidative stress and the accumulation of free radicals results in neuronal damage in AD. There are several studies evaluating the effects of antioxidative compounds on AD. Vitamin E and selegeline appear to delay progression. Research continues on the use of antioxidative vitamins and large US studies are underway to clarify the role of vitamin E in AD prevention.16^{, 30} A number of studies have evaluated selegeline for the treatment of AD. Most of these studies show some improvement in cognition, however there is very little evidence to support global improvements in cognition, functional ability and behavior. In a metanalysis of 15 selegiline trials, authors concluded that there was insufficient evidence to recommend its use for AD.15  A chochrane review of selegeline for AD concluded that there may be some benefit in cognition and its use may be promising. However, at present there is insufficient evidence to recommend its use in practice.17

§  Hormones. The attention and potential uses of hormone replacement therapy to treat AD is derived from epidemiological, clinical, and neuropathological observations and are still ongoing. Women are at a higher risk of developing AD than men since women are estrogen deficient post menopause whereas men benefit from estrogen as testosterone undergoes aromatization to estradiol. Estrogen is considered to have numerous beneficial properties some of which were thought to be antioxidant and anti-inflammatory  properties, interactions with neurotransmitters such as acetylcholine and its ability to alter apolipoprotein which could lower the risk of developing AD. Unfortunately, no studies to date have demonstrated a positive impact on improving the biological course of AD. Studies are still ongoing and need to assess the type of HRT administered, timing of HRT in AD, effect of HRT with cholinergics. Currently, there is insufficient evidence for HRT in AD management.16^,17

Other Agents. Various other pharmacological agents to treat AD are being studied. Gingko Biloba, a plant extract that contains numerous pharmacological properties, some of which are thought to be antioxidative, anti-inflammatory or neurotransmitter modulators. Current research suggests that the use of Gingko Biloba provides smaller effects that that of cholinergics. Also, it is currently unknown which of the active components of this alternative compound contributes to cognitive enhancing effects. Furthermore, the compound is a non-regulated supplement in several countries and standardized preparations are not available.