K. Farcnik, MD, FRCP(C), Psychiatrist, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.
M. Persyko, PsyD, CPsych, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.

Significant work has been done in the treatment of Alzheimer disease (AD) since cholinesterase inhibitors (CI) were approved in Canada five years ago. This has led to a better understanding of these drugs in terms of their different properties, therapeutic efficacy and indications for switching, and their use has since been extended to the treatment of AD with vascular pathology. Other treatments for AD, such as estrogens and non-steroidal anti-inflammatory drugs (NSAIDs), have also been evaluated further, while newer treatments, including a vaccine for AD, are currently in development. Although research outcomes have not always been positive, a significant effort is being made to achieve greater impact in a disease that is becoming ever more prevalent.

Cholinesterase Inhibitors
Currently, the CIs are the only class of drugs that have been proven efficacious in the symptomatic treatment of AD.¹ There are two types of CIs: acetyl and butyryl. Butyrylcholinesterase levels in the brain increase with the progression of AD, whereas levels of the enzyme acetylcholinesterase decrease.² The CIs approved in Canada that have demonstrated efficacy as well as a favourable safety profile are donepezil, rivastigmine and galantamine.

It is well known that aging is often associated with a poor immune response and a vulnerability to respiratory tract infections. It is also well recognised that nutritional status plays an important role in immune impairment, especially in the elderly. Vitamin and nutrient supplementation is thus often encouraged in the elderly under the assumption that it can only boost health, including their immune response. However, supplementing the diet with vitamin E may actually have an adverse effect on the severity of respiratory tract infections in the elderly, according to a recent Dutch study.

The investigators randomized 652 well-nourished, noninstitutionalized individuals from the Netherlands, 60 years or older, to physiological doses of either multivitamin-minerals, 200mg of vitamin E, both or placebo. The incidence and severity of self-reported acute respiratory tract infections were assessed by telephone with a nurse, home visits and microbiological and serological testing at 15 months.

Those participants taking the multivitamin-mineral supplements reported no increased rate or severity of infection. The vitamin E-users also did not report a greater incidence of infections, but they did suffer from greater severity compared to those who were not taking vitamin E. Among those randomized to vitamin E, illness duration was extended by five days and the number of symptoms experienced was six compared to four in non-users. Furthermore, 36.7% suffered from fever and 52.3% had their daily activities restricted, compared to only 25.2% and 41.1% of participants who did not take vitamin E respectively.

The study group concluded that neither daily multivitamin-mineral supplementation at physiological doses nor 200mg of vitamin E showed favourable effects on incidence and severity of acute respiratory tract infections in this group of elderly. Rather, they observed several adverse effects of vitamin E on illness severity. They suggested that further investigation of the effect of multivitamins and minerals in older persons with suboptimal plasma concentration of vitamins would be valuable. In the meantime, perhaps elderly people who are already well nourished should take caution when supplementing their diets with vitamin E.

Source

1. Graat JM, Schouten EG, Kok FJ. Effect of daily vitamin E and multivitamin- mineral supplementation on acute respiratory tract infections in elderly persons. JAMA 2002;288:715-21.

…and Ginkgo for Memory Enhancement

There have been many claims that the herb ginkgo, available as an over-the-counter dietary supplement, can improve memory, attention and other mental functions in as little as four weeks. Although the herb is marketed towards both those with and without significant cognitive impairments, these claims have thus far only been supported by studies of cognitively impaired clinical populations, such as patients with Alzheimer disease. A recent randomized, controlled, double-blind study now challenges earlier notions that ginkgo facilitates performance on learning, memory, attention and concentration in healthy elderly adults.

To evaluate ginkgo's potential as a memory enhancer, 230 healthy volunteers aged 60 to 82 years were randomly assigned to receive either 40mg of ginkgo or placebo three times daily with meals for six weeks. One day before randomization, and six weeks later, participants underwent neuropsychological evaluation, including tests of memory, learning, attention and concentration, and expressive language. Volunteers also provided a self-assessment of their own memory, and each of them had a close companion evaluate their overall change in memory.

After six weeks, data showed that ginkgo did not enhance performance on standard neuropsychological tests of learning, memory, naming and verbal fluency, or attention and concentration. Moreover, there were no differences between the gingko group and those taking placebo on the subjective self-reports of memory function or on the global ratings made by their companions. Both groups showed improved performance at six weeks, most likely because they became more familiar with the evaluations the second time around.

Marketers of gingko for the enhancement of memory promise positive results in four weeks. Although it is possible that the memory-boosting powers of ginkgo take longer than the six-week period used in this study, it can be concluded that healthy, elderly adults will not benefit from this supplement if they take it according to the manufacturer's suggestions.

Source

1. Solomon PR, Adams F, Silver A, et al. Ginkgo for memory enhancement: A randomized controlled trial. JAMA 2002;288:835-40.

Jenny F.S. Basran, BSc, MD, and David B. Hogan MD, FACP, FRCPC
Division of Geriatric Medicine, University of Calgary, Calgary, AB.

Introduction
Recently, there has been growing interest in the use of vitamins for the treatment of various health conditions. One study has estimated that 35-54% of older Canadians take some form of vitamin or mineral supplement.¹ Oxidative stress has been theorized to be an important contributor to select conditions, particularly those involving the cardiovascular and central nervous systems. Vitamin E is the only fat-soluble, chain-breaking antioxidant found in biological membranes⁴ and, therefore, has been investigated for its use in the treatment of ischemic cardiovascular disease in recent landmark studies such as the Heart Outcome Evaluation Study (HOPE)² and Heart Protection Study (HPS).³

How Does Vitamin E Work?
Vitamin E is a generic term for chemical derivatives of tocopherol and tocotrienol.⁵ There are eight naturally occurring forms, but only a-tocopherol is found in human plasma, has the highest bioactivity and is the form used for medicinal purposes. a-tocopherol is found naturally in vegetable oils, almonds, sunflower seeds, walnuts, sweet potato, liver, wheat germ and egg yolk.⁶ Synthetic forms are available as vitamin capsules and in fortified foods.

Thirty men and women received vitamin E supplements daily for 8 weeks, while others received placebo, in a study to determine the potential antioxidant effects of vitamin E. Previous studies have suggested that vitamin E supplementation may help protect against illnesses such as cancer and Alzheimer's disease, which are believed to result from accumulated free radical damage to tissues. Physicians measured the impact of vitamin E on three indices of lipid peroxidation, an indicator of oxidative stress in cells and tissues. These indices included urinary 4-hydroxynonenal (4-HNE), and two isoprostanes, iPF2-III and iPF2-VI, which were measured by gas chromatography and mass spectrometry. The study failed to find an impact of vitamin E on any of the three measurements.

Source

1. Meagher, E.A. et al. Journal of the American Medical Association. 2001;285:1178-1182.

Extracts from the leaves of the Ginko biloba tree and Vitamin E are just two of the therapies being investigated for the treatment of Alzheimer's Disease

Neil Fam, BSc, MSc

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized clinically by a gradual onset of progressive memory loss with deterioration in patients' social and occupational function. Changes in mood, behaviour and perception are also problematic aspects of the disease. Neuropathologically, AD is associated with the formation of amyloid plaques and neurofibrillary tangles, with impaired synaptic function and neuronal cell death. In particular, patients with AD suffer the loss of cholinergic, noradrenergic and dopaminergic neurons. Loss of acetylcholine neurotransmission in brain areas involved in learning and memory is thought to underlie many of the cognitive symptoms of AD. This concept forms the basis of current therapeutic strategies which aim to increase available acetylcholine levels in the brain by inhibition of acetylcholinesterase.