Both anosmia (loss of smell) and anosognosia (lack of awareness or insight of a deficit) appear to be strongly associated with higher risk of development of Alzheimer’s Disease (AD).^1,2

In a study involving 90 patients with mild cognitive impairment (MCI) followed for up to 2 years, subjects with low olfaction scores were significantly more likely to develop AD than those with high scores (40% vs 0%, p<0.001).  In the same study, all patients with anosognosia (accounting for 84% of the low olfaction group) developed AD irrespective of higher baseline Mini Mental State Examination (MMSE) score. ¹

A 2017 meta-analysis of olfactory dysfunction in MCI also found a significant association between olfactory deficits and MCI with tests of odor identification having larger effect sizes than those of odor detection threshold or memory.²

As for possible mechanisms, anosmia in AD is felt to be due to degeneration of neurons of the entorhinal- hippocampal-subicular complex associated with an observed increase in neurofibrillary tangles.³ Interestingly, the density of tau tangles in the entorhinal cortex have been shown to be inversely related to odor identification.⁴  There also seems to be a correlation between anosognosia and atrophy in the dorsal anterior cingulate cortex, reflected by the finding of hypometabolism on PET-FDG images⁶.

Bonus Pearl: Did you know that anosmia and ageusia (loss of sense of taste) are also common nonmotor feature of Parkinson’s Disease and can predate onset of motor symptoms by years? ⁵

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References

1. Devanand DP, Michaels-Marston KD, Liu X, et al: Olfactory Deficits in Patients With Mild Cognitive Impairment Predict Alzheimer’s Disease at Follow-Up. Am J Psychiatry, 2000; 157:1399-405 https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.157.9.1399                                   
2. Roalf DR, Moberg MJ, Turetsky BI, et al: A quantitavie meta-analysis of olfactory dysfunction in mild cognitive impairment. J Neurology Neurosurg Psychiatry 2017;88:226-232. https://jnnp.bmj.com/content/88/3/226
3. Talamo BR, Rudel R, Kosik KS, et al: Pathological changes in olfactory neurons in patients with Alzheimer’s disease. Nature 1989; 337:736–739. https://doi.org/10.1038/337736a0 
4. Wilson RS, Arnold, SE, Schneider JA, et al: The relationship between cerebral Alzheimer’s disease pathology and odour identification in old age. J Neurol Neurosurg Psychiatry, 2007;78:30-5. https://doi.org/10.1136/jnnp.2006.099721
5. Tarakad A, Jankovic J: Anosmia and Ageusia in Parkinson’s Disease. International Review of Neurobiology, 2017; 133:541-556https://doi.org/10.1016/bs.irn.2017.05.028
6. Guerrier L, Le Men J, Gain, A, et al: Involvement of the Cingulate Cortex in Anosognosia: A Multimodal Neuroimaging Study in Alzheimer’s Disease Patients. Journal of Alzheimer’s Disease 2018; 65:443-453. https://content.iospress.com/articles/journal-of-alzheimers-disease/jad180324

Contributed by Jackie Fairchild MD, Mercy Hospital-St. Louis, St. Louis, Missouri

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy, its affiliate healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!