Alzheimer’s Disease – Prevention or Delay by Altering Lifestyle?by Shaheen E Lakhan, MD, PhD, MEd, MS, FAAN | August 11, 2006
We now know several genes involved in the origin of Alzheimer’s disease (AD). Thus, we are now in an era where genetic testing may prove useful to complement diagnosis in individuals that may have Alzheimer’s disease, in the early detection of the disease in patients with mild cognitive deficits, and for predicting onset of the disease in those that do not have any symptoms currently. Indeed, it is now pertinent to ask the question: Can you prevent or delay Alzheimer’s disease (AD) if you changed your lifestyle?
AD is the most common cause of dementia in the United States. It will become even more common in the coming decades, as the number of elderly in the population increases. The search for new genes and genetic markers for AD is critical for identifying risk and improving the understanding of the disease’s molecular pathophysiology.
Indeed, the unearthing of AD genes, even those mutations that cause very rare cases of early-onset AD, helped inform our understanding of the amyloid hypothesis. It also help channel the search for effective treatment in the appropriate direction and opened the way for understanding the roles of new non-genetic factors in AD, behaviors or conditions that can be altered to reduce the risk of developing AD.
Alzheimer’s disease is a genetically complex and heterogeneous disorder mostly affecting the elderly, with just about 5% patients affected by bthe condition being less than 60 years old at onset. In individuals with this early-onset Alzheimer’s disease, autosomal dominant inheritance is often involved. We now know that three genetic defects cause early-onset Alzheimer’s disease in families.
The first gene genetically linked with this form of Alzheimer’s disease was the amyloid precursor protein (APP) gene on chromosome 21, with at least six different pathogenic mutations influenced by APOE genotype. The second gene is Presenilin-1 (PSEN1) on chromosome 14, with 50 different Alzheimer’s disease mutations that account for most of Alzheimer’s disease before age 50 and does not seem to be modified by APOE genotype. The third is Presenilin-2 (PSEN2) on chromosome 1 for which only two different familial Alzheimer’s disease mutations have been identified. It may be modified by APOE genotype.
On the contrary, late-onset Alzheimer’s disease, which develops after age 60, has been associated with genetic risk factors, rather than causative genes, the only confirmed genetic risk factor being the 4 allele apolipoprotein E gene (APOE-4) on chromosome 19, which has three normally occurring alleles, named 2, 3, and 4. Finding genes that add to the risk of developing the disease is hard because the condition is common, especially at advanced ages making chance familial clustering quite possible. Multiple genetic and non-genetic Alzheimer’s disease risk factors may actually occur in a single family.
Besides, since it occurs very late in life, many patients do not survive the age of risk of AD, hence assessment of its familial pattern is difficult. Other causes of cognitive decline, for example, stroke are commoner in older than younger persons, hence more likelihood of diagnostic errors. Current research indicates that APOE may act primarily as a modifier of age at onset in otherwise susceptible patients.
Observations of identical twins discordant for Alzheimer’s disease or with large differences in age at onset indicate that environmental factors are also involved in the development of AD.
Some health and lifestyle changes can lower the risk of developing AD. There is increasing evidence to show that some of the same risk factors that promote heart disease and stroke may promote, or at least worsen, the course of AD. Thus, the presence of cerebrovascular disease may predict a more rapid course in patients with dementia. Elevated midlife cholesterol, diabetes, and high midlife systolic blood pressure are also risk factors for developing AD. Changing your lifestyle to prevent these conditions might also be helping you prevent AD in the future.
By: Dr. George B. Obikoyz
Editor: Shaheen Lakhan
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