Decreased sense of smell may indicate early dementia

Decreased sense of smell appears to be linked to the onset of Alzheimer's, according to an article published in JAMA Neurology.

Loss of sense of smell may indicate onset of some types of dementia, researchers say.

Previous research has associated olfactory loss, or anosmia, with cognitive decline, mild cognitive impairment (MCI) or Alzheimer's disease (AD). It may also be a marker for Lewy body and vascular dementia.

Autopsy studies have linked a loss of ability to identify odors with the plaques and tangles in the olfactory bulb, entorhinal cortex and the cornu ammonis regions of the hippocampus.

Markers of early detection can help prevent or delay these diseases, and olfactory impairment may be an important clinical marker and predictor of these conditions, helping to identify those at risk.

Rosebud Roberts, of the Mayo Clinic in Rochester, MN, and coauthors assessed the sense of smell of 1,430 cognitively normal individuals, with an average age of 79.5 years; approximately half were men and half were women.

The participants were enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010, and were clinically evaluated at baseline and every 15 months through 2014.

Olfactory decrease matches increase in memory loss

The test they used involved six food-related and six non-food-related smells (banana, chocolate, cinnamon, gasoline, lemon, onion, paint thinner, pineapple, rose, soap, smoke and turpentine). Participants had to scratch, sniff and select one of four possible options, for a score to be computed.

Over an average of 3.5 years of follow-up, the authors identified 250 new cases of MCI among the 1,430 participants.

There was an association between a decreasing ability to identify smells - as measured by a decrease in the number of correct answers in the smell test score - and an increased risk of amnestic MCI (aMCI). There appeared to be no association between a decreased sense of smell score and nonamnestic MCI (naMCI), which can affect other thinking skills.

People with aMCI have memory problems more severe than normal for their age and education but not serious enough to affect daily life; naMCI is characterized by impaired thinking skills other than memory, such as trouble planning and organizing or poor judgment.

The authors also reported 64 dementia cases among 221 individuals with prevalent MCI. A decrease in the frequency of any or AD dementia was associated with increasing scores on the smell test. The worst smell test score categories were associated with progression from aMCI to AD dementia.

The findings suggest an association between olfactory impairment, incidental MCI and progression from aMCI to AD dementia, and confirm previous studies linking olfactory impairment with cognitive impairment in late life.

Neurodegenerative changes at the root of the problem

Potential explanations for the current findings involve neurodegenerative changes in the olfactory bulb and brain regions that involve memory and sense of smell.

Fast facts about dementia

• 10-20% of over-65s are estimated to have MCI
• Alzheimer's accounts for 60-80% of all dementias
• 10% of dementias are vascular.

The olfactory bulb is thought to be involved because smell loss occurs only in neurodegenerative conditions where there is olfactory pathology, such as AD and Parkinson's disease.

Neurofibrillary tangles, features of AD, have been found in the olfactory bulb and tracts before the onset of symptoms, suggesting that olfactory deficits may be early markers of the disease.

AD symptoms in the entorhinal cortex, hippocampus and other temporal regions may limit ability to store and retrieve memories of smell, and thereby to identify odors correctly.

Cholinergic deficits are involved in olfactory loss in AD dementia and Parkinson's disease. These deficits could help distinguish between neurodegenerative diseases with olfactory impairment, such as Parkinson's disease and AD, and those without, such as progressive supranuclear palsy.

Reduced levels of choline acetyl transferase and dopamine in the olfactory tubercle and other brain regions may also play a role, as well as decreased norepinephrine related to damage or neurodegeneration in a source of norepinephrine to the olfactory bulb.

Limitations include not directly assessing odor detection; but this was felt unlikely to bias the findings because odor detection tests correlate highly with odor identification tests, and patients with AD and a number of other neurodegenerative diseases demonstrate deficits in both detection and identification.

The authors conclude:

"Clinical implications of our findings are that odor identification tests may have use for early detection of persons at risk of cognitive outcomes."

References:

1.  Association between olfactory dysfunction and amnestic mild cognitive impairment and Alzheimer disease dementia, Rosebud O. Roberts et al,JAMA Neurology, doi:10.1001/jamaneurol.2015.2952, published online 16 November 2015. 
2.  JAMA news release, accessed 16 November 2015.
Additional sources:
3.  Albert Einstein College of Medicine, Mild cognitive impairment, accessed 16 November 2015.
4.  Alzheimer's Association, Mild cognitive impairment, accessed 16 November 2015.
5.  Alzheimer's Association, 2014 Alzheimer's disease facts and figures, accessed 16 November 2015.