Wendy S. Meschino, MD, CCFP, FRCPC, FCCMG
Department of Genetics,
North York General Hospital,
Toronto, ON.

The last decade has seen important gene discoveries for early-onset, autosomal dominant forms of Alzheimer disease and other dementias. The genes include presenilin 1, presenilin 2 and amyloid precursor protein (APP) for Alzheimer disease, the tau gene for frontotemporal dementia (FTD) and notch3 for CADASIL. Testing for one or more of these genes is available in research laboratories in Canada and in a private US lab. Testing for presenilin 1 is indicated for patients affected with early-onset (< 60 years) Alzheimer disease. If an affected family member is unavailable (i.e. deceased), testing an unaffected first-degree relative can be considered when there are two or more affected early-onset cases in the family.

Patients requesting pre-symptomatic (predictive) testing should be referred for appropriate genetic counselling, including a full discussion of the risks and benefits of predictive testing. The following points should be considered before proceeding: Is the choice to have testing informed and free from coercion? What are the reasons for knowing or not knowing? What are the potential effects on other members of the family? Is there a potential for insurance, employer or other forms of discrimination?

For the majority of Alzheimer disease (95%), which occurs after age 60, no major dominantly inherited genes have been found. In most cases, the disease occurs sporadically in families. However in approximately 15-25%, the etiology has a complex genetic basis with both inherited and environmental modifying factors. One such genetic modifier is the e4 allele of the apolipoprotein E gene, which has been associated with a decreased age of onset, especially when homozygous. As it is neither necessary nor sufficient for onset of the disease, testing for e4 has limited utility and is not recommended in the pre-symptomatic situation. A search for other late-onset Alzheimer genes is in progress. In this regard, genetic testing on a research basis may be considered when samples can be obtained from two or more affected family members.

Cynthia Jackevicius, BScPhm, MSc
Practice Leader,
Pharmacy Department,
Associate, Women's Health Program,
University Health Network-Toronto General Hospital,
Assistant Professor,
University of Toronto, Toronto, ON.

Coronary heart disease (CHD) is a major economic burden on the health care system, with the total cost of the morbidity and mortality associated with cardiovascular disease in Canada estimated at $18.0 billion in 1994.¹ Effective prevention and treatment decrease morbidity and mortality associated with CHD. A controversial issue in recent years has been whether the reduction of cholesterol results in a decline in subsequent CHD events and mortality in patients older than 65 years of age.² Several observational studies have suggested that elevated cholesterol levels may not be a significant cardiovascular risk factor in older people. However, a recent study investigated this hypothesis and found that after adjustment for risk factors and indicators of frailty, such as low serum albumin, elevated total cholesterol levels do predict increased risk for death from CHD in older adults.³

Three recently published, landmark trials focusing on the benefits of statins in the prevention of secondary coronary events showed that statins improve patient outcomes with minimal adverse effects.