Alzheimer's Disease Overview

Alzheimer's Disease is an increasingly common cause of disability among older Americans. The disease currently affects 5 million people and is expected to triple by 2050. Although it occurs primarily in people over 65 years of age (about 1 in 8 people) and a staggering 42% of those over 85*, it can sometimes afflict those in the 50’s and even 40’s.

Symptoms develop gradually over time, starting with a memory loss which may not even be noticed by the sufferer but recognized by family members who bring it to a doctor’s attention. By the time they seek help, most patients are already experiencing other symptoms such as disorientation, mood and personality changes, and language difficulty.* As the disease progresses, other symptoms begin to emerge, including disregard to personal care, incontinence, repetitive behavior and wandering. At its worst, AD can result in death brought on by the loss of basic functions such as swallowing* and refusal to eat or drink.*

There is no definitive chemical or imaging tool that can diagnose AD in a living person. Instead diagnosis is made by identifying characteristic symptoms such as memory loss and cognitive impairment, and by excluding other causes of dementia*. The primary hallmark of the disease, neurofibrillary tangles and amyloid plaques, can only be identified accurately through microscopic examination of brain tissue during an autopsy.

Because it is such a slowly progressing disease with no early detection tests available, some researchers are studying if short telephone questionnaires, which people can take at regular intervals, can reveal a decline in performance as an indication of age-related dementia. Other researchers are studying the loss of certain senses, such as the inability to identify the smell of lemons and lilacs, as a predictor of AD.*

The underlying cause of AD is not yet known, but both genetic and environmental factors are thought to play a role. A person is up to three times more likely to develop it if he has an immediate family member with the disease.* This number increases as more family members are affected.

Although the precise mechanism is unknown, early onset AD, a rarer form of the disease which affects people in early middle age, is associated with at least three genes. Inheriting one of these mutated genes means a very high chance of developing the disease before age 65.* But only about 7% of early onset AD cases are familial.*

Women who are under the age of 35 when they give birth to a Down Syndrome baby are also more likely to develop early onset AD. One hypothesis is that these women’s bodies, including their eggs, are prematurely aging, thus suffering from age-related disorders at a younger age. Women who are over 40 when they have a Down offspring do not have an elevated rate of early onset AD.

Both early onset and late onset AD are associated with diabetes. While the exact connection is not yet known, it is thought that the insulin resistance experienced by diabetics also affects glucose bioavailability in the brain.

Glucose is the brain's fuel. Insulin allows brain and other cells to take in glucose and convert it to energy. One function of insulin in the brain is to bind to receptors thereby allowing memories to form. But in diabetics, the pancreas does not create any insulin (Type 1), or the body is insulin-resistant (Type 2), meaning cells do not use insulin properly. Their cells are starved of glucose while the pancreas tries to compensate by producing even more insulin. The brain responds to this increased level of insulin and blood glucose by slowing the transport of glucose across the blood brain barrier, further reducing the amount of glucose feeding brain cells and causing memory impairment similar to Alzheimer’s, and possibly cell death.

Since the Alzheimer’s/diabetes correlation has been found in numerous studies, research is being done to test if treatments for diabetes can also be used to treat or ameliorate the effects of the other. This is in addition to the dozens of drugs in Phase I or Phase II trials for FDA approval.* Five drugs have already received approval, and although they can slow the progression of AD to varying degrees, none of them cure patients or treat the underlying cause.*

But scientists are following new avenues of research. Research has shown that the brain can be deprived of glucose through an ADDL (amyloid B-derived diffusible ligand) protein. These proteins, which appear to accumulate as Alzheimer’s progresses, bind to insulin synapses, stopping insulin receptors from gathering at the synapses and depriving cells of glucose, thus preventing the formation of memories.*

Unlike amyloid plaques which nearly every older person has, AD or not, post-mortem studies have shown highly elevated ADDL levels in AD patients but in few non-patients.* One upshot of this is that it may be possible to use ADDL levels in blood or cerebrospinal fluid to at last provide a way to biologically diagnose AD in living patients.* Even more significant, it may be possible to treat certain cases of AD by lowering ADDL levels and returning neurons to normal function.*

With 16 million Americans expected to have Alzheimer’s Disease by 2050, there is a strong need for further research into the cause and treatment of the condition. An aging population, combined with increasing rates of obesity and Type II diabetes, only raises the level of urgency.