Poor Sense of Smell Correlates with Increased Mortality in Older Individuals

It is quite easy to find correlations between the many varied aspects of aging. People age at different rates, largely due to differences in lifestyle choices: exercise, calorie intake, smoking, and so forth. Genetics are less of an influence. While there is tremendous interest in the genetics of aging, I have to think that this is something of a case of a hammer in search of a nail. This is an era of genetic technologies and genetic data, in which the cost of the tools has fallen so low and the scope of the capabilities has expanded so greatly that everyone is tempted to use it in every possible circumstance. Yet outside of the unlucky minority who suffer severe inherited mutations, genetic variations only become important in later life, and even then the contribution of genetics to life expectancy is much smaller than that of lifestyle choices.

Nonetheless, the point is that different people age at different rates. For any given person, however, the many aspects of aging are fairly consistent with one another - nothing races ahead in isolation. Aging is a body-wide phenomenon of multiple processes of damage accumulation that proceed in an entangled fashion, feeding one another and all contributing to systemic downstream consequences, such as chronic inflammation or vascular dysfunction. In this sort of a system, if any one organ or biological system is more aged and damaged in a given individual, then it is very likely that all of the others are as well. This works for correlations with mortality as well as specific age-related diseases or metrics.

In the research results noted below, a poor sense of smell in older individuals correlates with a significantly raised risk of mortality over a ten year horizon. For the reasons given above, this shouldn't be terrible surprising. Loss of sense of smell is a reflection of levels of neurodegeneration, loss of function in the brain. That in turn tends to match up with loss of function elsewhere in the body, particularly in the cardiovascualar system. Failing sense of smell is further specifically associated with Alzheimer's disease, as the olfactory system in the brain is where the condition starts. You can look at the work of Leucadia Therapeutics for evidence that Alzheimer's disease begins in this way because clearance of cerebrospinal fluid in that part of the brain is impaired with age, leading to increased molecular waste and cellular dysfunction.

Poor Sense of Smell and Risk for Death in Older Adults

Many older adults have a poor sense of smell, which can affect their appetite, safety, and quality of life. It is also associated with increased risk for death and may be an early sign of some diseases, like Alzheimer's disease and Parkinson's disease. Most previous studies have studied people with a poor sense of smell for relatively short periods of time, and they did not examine whether there are differences by race or sex. We also need a better understanding of the factors that might explain the relationship between poor sense of smell and increased risk for death.

Researchers analyzed data on the members of an ongoing study that was done in 2 communities in the United States (Memphis, Tennessee, and Pittsburgh, Pennsylvania). There were 2289 adults, aged 71 to 82 years, at baseline. The participants completed a Brief Smell Identification Test (BSIT). As part of the test, they smelled 12 common odors and were asked to identify each odor from 1 of 4 options. Each correct response was given a point. Using the BSIT scores, the researchers classified the participants as having good, moderate, or poor sense of smell. Participants attended several clinical study visits, where they were examined and had cognitive tests. In these visits, patients were identified as having dementia or Parkinson's disease, and staff measured participants' body weights. The main end points for the study were death from any cause; death from dementia or Parkinson's disease; and death from cardiovascular disease, cancer, or respiratory causes.

A poor sense of smell was associated with older age, male sex, black race, alcohol drinking, and smoking. It was also associated with dementia, Parkinson's disease, and chronic kidney disease. Participants with a poor sense of smell had a nearly 50% higher risk for death at 10 years. A poor sense of smell was also associated with increased risk for death from dementia or Parkinson's disease and death from cardiovascular disease. The investigators did some exploratory statistical analyses and found that weight loss and a history of dementia or Parkinson's disease could explain only part of the relationship between poor sense of smell and death.

Relationship Between Poor Olfaction and Mortality Among Community-Dwelling Older Adults: A Cohort Study

To assess poor olfaction in relation to mortality in older adults and to investigate potential explanations, 2289 adults aged 71 to 82 years at baseline underwent the Brief Smell Identification Test in 1999 or 2000 (baseline). All-cause and cause-specific mortality was assessed at 3, 5, 10, and 13 years after baseline. During follow-up, 1211 participants died by year 13. Compared with participants with good olfaction, those with poor olfaction had a 46% higher cumulative risk for death at year 10 and a 30% higher risk at year 13.

However, the association was evident among participants who reported excellent to good health at baseline but not among those who reported fair to poor health. In analyses of cause-specific mortality, poor olfaction was associated with higher mortality from neurodegenerative and cardiovascular diseases. Mediation analyses showed that neurodegenerative diseases explained 22% and weight loss explained 6% of the higher 10-year mortality among participants with poor olfaction.


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