What causes Alzheimer’s disease to start? What makes it more likely to affect some people rather than others?
There is no known single cause of Alzheimer’s disease. However, research has identified many possible, probable, and known risk factors.
Several genes are now known to confer risk – or in some cases, protect against – Alzheimer’s disease. This means that Alzheimer’s can run in families. For example, inheriting one copy of the APOE4 gene variant, which is found in about a quarter of the population, will cause up to four times the normal risk of developing Alzheimer’s. Inheriting two copies (one from each parent) will raise risk up to ten times normal levels.
Known genetic factors account for a small percentage of all Alzheimer’s cases, but current research supported by CAF and others indicates far more genetic influence than was previously known. Many candidate genes are currently being discovered and studied for their role in the disease. The genes we know about account for a larger percentage of early-onset cases. The rare Presenilin 1 and 2 genes, for instance, virtually guarantee development of early-onset Alzheimer’s.
Individuals with Down syndrome almost always develop early-onset Alzheimer’s disease. Down syndrome occurs in those carrying an extra copy of chromosome 21. This chromosome happens to include the APP gene, which controls Abeta production, a major factor in Alzheimer’s disease pathology.
Health and environmental factors
The following factors are also thought to affect risk for Alzheimer’s disease:
Age is the number one risk factor for Alzheimer’s. After age 65, risk tends to double about every five years, reaching almost 50 percent by age 85. In rare cases, the disease can also strike much earlier in life.
Cardiac and vascular health, including stroke
Sex - Some data suggest that more women than men are diagnosed with Alzheimer’s. However, that number may be affected by the fact that women tend to live longer than men, and risk for Alzheimer’s increases with age. Recent research suggests that estrogen and menopause may be involved in raising risk for the disease in women.
Social isolation - Depression and social isolation are risk factors for Alzheimer’s disease. There is no evidence to suggest that antidepressants, which reduce these conditions, have a positive effect on Alzheimer’s once the disease has already begun.
Sleep patterns - With age, the sleep/wake cycle starts to break down, with older adults progressively getting less and less sleep. Investigators are considering studies of whether chronic sleep loss in young and middle-aged adults increases risk of Alzheimer’s disease later in life.
Research by David Holtzman, M.D., has shown that when genes regulating sleep/wake cycles are deleted in mice, this causes cognitive decline.
Anesthesia - Research by Zhongcong Xie, M.D., Ph.D. has shown that the general inhalant anesthetic isoflurane can accelerate Alzheimer’s pathology. As such, we recommend using desflurane instead. However, there is not yet enough data to suggest isoflurane should no longer be used.
Head trauma - Traumatic brain injury has been linked with increased risk for Alzheimer’s disease, as well as other neurodegenerative diseases including Parkinson’s and chronic traumatic encephalopathy.
Stress levels - Stress has been shown to accelerate Alzheimer’s pathology in animal models. Research has not yet been conducted to examine this effect in humans.