Many of us start to lose our sense of smell as we age.

For some, however, a diminished sense of smell could signal significant health problems, including Parkinson's and Alzheimer's diseases. It turns out that other neurodegenerative diseases also are accompanied by similar reductions in the sense of smell, although often not as severe.

Richard L. Doty, director of the Smell and Taste Center at the University of Pennsylvania's Perelman School of Medicine, where he is also a professor of otorhinolaryngology (ear, nose and throat disorders), has wondered whether these losses have similar causes and whether that information could serve as an early warning sign for neurodegenerative disease.

In a review published online in June in the Lancet Neurology, a clinic neurology journal, he said there is evidence of a common link: damage to neurotransmitter systems in the front part of the brain.

He spoke to us recently about the sense of smell.

Many people lose their sense of smell, especially as they age. What are some common reasons?
The senses tend to drop off as we get older, so just as with hearing, smell loss with age is very common. Over the age of 80, three out of four people have a demonstrable loss. Between 65 and 80, half the population has demonstrable loss. Not total loss, just measurable change.

The reasons for this are multiple. As we go through life, we're exposed to viruses, bacteria, air pollution, things like that.  As a result, there is damage to the nasal epithelium in the higher recesses of the nose, where the olfactory receptors are located. The damage isn't consequential. However, over the years it accumulates, and at some point — usually after age 65 — we notice the change. Thus, every time we have a cold, a toll is taken. In the clinic, we see a lot of patients, mostly  in their 40s and 50s, who say they've had a terrible cold that has affected their taste, and six months later, their food still doesn't taste right, often like cardboard. The flavor of food is connected to the sense of smell. Many people will recover, but some don't. It depends on the amount of cumulative damage.

Another contribution to age-related loss involves the olfactory nerve fibers. As they go from the nasal cavity into the brain, they basically go through holes in the bone of the skull. Those holes can ossify, or close off, in some people as they get older, and the nerves get pinched off.  Another cause of a diminished sense of smell is changes in blood flow into the olfactory area.

What about neurodegenerative diseases?
There are a number of neurodegenerative diseases in which smell loss is an early sign of the disease. For example, most people that have Parkinson's disease have some loss of  smell. One of the problems is that unless you have severe loss, you often don't notice a problem. With Parkinson's, only about 15 percent of people are aware of a decreased smell function until they get tested.

Then again, some people with Parkinson's recognize their smell loss 20 years before they ever get the motor problems. Longitudinal studies suggest that most people will have smell loss five to seven years before both motor problems and the diagnosis.

With Alzheimer's, among people who have what's called mild cognitive impairment — a sort of precursor to the disease — those that have smell loss at that stage are more likely to go on to get Alzheimer's.

Tell us about the Lancet article.
My hypothesis, in the Lancet article, is that certain neurotransmitter systems in the brain's olfactory areas are diminished at the early stages of these diseases.

For the article, we looked at a large number of different neurodegenerative diseases. In these cases, a very likely reason for their loss of smell is a decrease in the function of a major neurotransmitter called acetylcholine. Neurotransmitters are chemicals that send signals throughout the brain. Those patients with lots of loss of smell have lots of damage to the brain region that is the source of acetycholine.

In essence, we believe that the pathology of a number of such diseases begins years before they actually get diagnosed. Whether the neurotransmitter changes reflect the beginning of the disease process or whether damage to the neurotransmitters causes the disease in genetically susceptible people is the $64,000 question. So we believe these diseases are beginning years ahead of when they actually get diagnosed. In the earliest stages of these diseases, the changes that are occurring, including a decrease in smell function, are possibly caused by changes in certain neurotransmitter systems.

That's important. With Alzheimer's, you can give a drug that facilitates acetylcholine transmission. The drugs are not as good as one would hope, because usually by the time one reaches the stage of disease that's clinically diagnosed, too many brain cells have been damaged. But from a research perspective, being able to detect these diseases early leads to the possibility that certain interventions could occur to limit damage or slow down the disease process.

You've developed an olfactory test. Should people get their sense of smell tested regularly, just as they do their vision and, as they age, often their hearing?
The average physician, even the average neurologist, doesn't test your sense of smell in any quantitative way. Back in the early 1980s, we developed here at Penn a smell identification test. Hundreds of thousands of people have now taken this test. It's standard in research. The downside is that most insurance companies don't pay for smell testing, although Medicare typically does pay.

Interestingly, in some cultures, smell testing is becoming more routine. I'm working with a pharmaceutical company in Japan that is pursuing this as an important thing to do in looking after the elderly and helping the elderly and their families deal with the onset of Alzheimer's.

Just like hearing loss, loss of the sense of smell can be problematic. Decisions have to be made about smoke detectors. There are concerns about not being able to detect spoiled food. There are many other issues related to safety and quality of life independent of neurodegenerative diseases.

But one has to be careful about the interpretation of smell loss. Just because someone has a decreased sense of smell doesn't mean they are bound to get a neurodegenerative disease. We also see people who think they have a major smell problem, but after testing, it turns out they're normal.

Is there anything that can be done about normal lessening of one's sense of smell?
Although it's difficult to follow, avoiding air pollution and minimizing sicknesses such as colds by hand washing and avoidance of people with colds can go a long way in minimizing damage to the olfactory receptors. There's some evidence that practicing smelling odors before bed at night and when you get up in the morning may help. We tell our patients to go to their pantry and find about a dozen bottles of herbs and spices — vanilla extract, licorice, anything that doesn't have an irritative effect. Sniff through these bottles twice before going to bed and twice after getting up in morning. There is evidence from both human and animal studies that this is effectual to some degree.