Anosmia (loss of smell) or hyposmia (lesser smell) may be an early and important symptom of Alzheimer’s disease before other symptoms begin. The rate of odor loss may be associated with an increased risk for developing Alzheimer’s. Anosmia may worsen as the disease progresses from early dementia to Alzheimer’s disease.
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Alzheimer’s disease is the most common type of dementia worldwide. At the heart of the pathology is atrophy (degeneration) of the brain, particularly the hippocampus and cortex caused by neuronal & synaptic loss. Neuronal loss occurs as a result of the buildup of amyloid-beta cells and neurofibrillary tangles of hyperphosphorylated-tau – two major pathological markers in Alzheimer’s disease.
Although the symptoms of Alzheimer’s disease are obvious as the disease progresses, early detection may be important in slowing down the disease – especially with the continued development of novel therapies or better disease management from early. The problem, however, is that early detection (biomarkers) is limited or difficult to assess in the clinic and a firm diagnosis can only be made after extensive clinical, neuroimaging, pathological and post-mortem examination. .
Loss of smell in Alzheimer’s disease
One American study found that older individuals (approximately 3000 people aged 57-85) with an unpleasant odor (hyposmia) were more than 2 times more likely to develop dementia within 5 years, non- independent of other risk factors. Those with the poorest olfactory discrimination (total anosmia) were the most likely to develop dementia within 5 years. The degree of olfactory deficiency was associated with the severity of depression ie, a slight deficiency associated with brain impairment in healthy control, and a high rate of Alzheimer’s deficiency.
Of all those assessed, 4.1% were subsequently diagnosed with dementia within 5 years and 47% were with olfactory dysfunction at the first assessment. This compared with 80% of those evaluated who had normal olfactory function did not develop depression within 5 years. In addition, a meta-analysis of 39 studies showed that a significant effect size (Cohens d = 1.73) was reported between odor loss and Alzheimer’s disease, although there is a high degree of heterogeneity – particularly between MCI and Alzheimer’s loss of smell.
Although odor loss is not considered a major symptom of Alzheimer’s disease, it is, nevertheless, one of the earliest symptoms present in patients (if it occurs). It’s also important to remember that odor loss alone is not a sufficient symptom of Alzheimer’s disease, and in fact it is also found in many other brain conditions including early Parkinson’s disease in particular, as well as in multiple sclerosis, amyotrophic lateral sclerosis and Huntington’s disease.
The development of disease-specific odor tests is essential to differentiate between diseases – if at all possible (more research is needed at this stage). Nevertheless, loss of smell is an important symptom that occurs in a number of brain conditions (as discussed). Therefore, if odor tests reveal deficiencies, it would be important to administer routine tests such as MMSE along with neuroimaging as a robust method in evaluating the earliest stages of Alzheimer’s.
In addition, hyposmia (bad smell) can be called normal age, however, the degree of hyposmia or anosmia, especially earlier than would be expected as part of aging is a strong indication of the greater ability to develop depression within a few. years since the onset of these symptoms – before any mental health problems begin to occur.
What causes odor loss in Alzheimer’s disease?
Just as amyloid plaques and neurofibrillary tangles contribute to neuronal and synaptic loss in the brain itself, they are also thought to be causative in olfactory dysfunction. Neuropathology is thought to occur in regions as the olfactory system begins before defects within the hippocampus and cortex occur. In addition, the olfactory system has limited autoimmune mechanisms and thus makes it more vulnerable to Alzheimer’s-related damage.
Based on these findings, a simple discriminatory odor test may be able to assess the risk of Alzheimer’s disease (or other brain conditions) before symptoms of disease begin to appear. These could be validated by other diagnostic tools such as clinical trials, biomarkers and neuroimaging, etc. Early identification can lead to early intervention with a higher chance of improved prognosis and long-term plan implemented.
In summary, odor loss could be an early and important biomarker of Alzheimer’s disease that occurs before the onset of any obvious mental deficits. Those with loss of smell in middle age are more likely to develop Alzheimer’s within a decade, and those with the greatest loss of smell (total loss) are at greatest risk. Thus, odor discrimination tests could be an easy and effective measure in evaluating the potential for the development of Alzheimer’s disease and allow for early interventions and management plans.