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Olfactory dysfunction as a biomarker for Alzheimer's disease

A decline in the sense of smell can indicate incipient dementia
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(Vienna, 12 November 2018) During the course of a medical dissertation being prepared at MedUni Vienna, the relationship was investigated between olfactory dysfunction and the development of Alzheimer's disease. Olfactory performance proved to be a better predictor of dementia than memory tests for the recall of names.

A large part of the current studies relating to Alzheimer's disease are concerned with early detection of the disease through the use of biomarkers. Diagnosing and treating the disease as early as possible improves the efficacy of future treatments to slow down its progression.

The preliminary stage of Alzheimer's disease is known as Mild Cognitive Impairment (MCI)," explains Elisabeth Stögmann, Head of the Outpatient Memory Clinic at MedUni Vienna’s Department of Neurology, "but the symptoms of Subjective Cognitive Decline (SCD) also presumably represent a prodromal phase of the disease in many cases."

It has been clear for some time that neuropathological changes, such as the deposition of pathological proteins like amyloid beta and phosphorylated Tau already exist several years before the onset of obvious cognitive impairment. These deposits must also exist in anatomical areas of the brain associated with the olfactory system long before break-out of the disease, explains Principal Investigator Johann Lehrner from the Neuropsychology Division of the Department of Neurology.

As part of a medical dissertation, the relationship between olfactory dysfunction and the development of Alzheimer's disease was investigated in SCD and MCI patients. The study collective consisted of 650 patients, including controls without any cognitive impairment as well as patients with SCD and MCI. Sniffin’Sticks were used to assess olfactory performance. 120 of the 650 patients then took part in a follow-on study after an average of two years, thus forming the longitudinal study population. At the time of the follow-on study, 12% of these patients met the diagnostic criteria for Alzheimer's disease.

Statistical evaluation of the study showed a significant correlation between impaired olfactory identification at the start of the study in patients with MCI and the presence of Alzheimer's disease at the time of the follow-on study. Olfactory performance proved to be a better predictor of dementia than memory tests for the recall of names (semantic memory).

According to Johann Lehrner, this finding could be seen as an indication that these patients experienced measurable changes to their sense of smell as a result of neuropathological changes, while largely retaining their semantic memory function.

Lehrner considers this to have potential for the early detection of Alzheimer's disease: "We intend to use this testing method for checking the human sense of smell in future large-scale studies for stratifying the risk of developing dementia, to establish whether it has a role to play in the early detection of Alzheimer's disease. There are also indications that specific olfactory training could positively influence the course of Alzheimer's disease."

Tahmasebi R, Zehetmayer S, Pusswald G, Kovacs G, Stögmann E, Lehrner J.: Identification of odors, faces, cities and naming of objects in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer´s disease: a longitudinal study. Int Psychogeriatr. 2018 Sep 21:1-13. doi: 10.1017/S1041610218001114. [Epub ahead of print]