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  • Review Article
  • Published:

Olfactory and other sensory impairments in Alzheimer disease

Nature Reviews Neurology volume 15, pages 11–24 (2019)Cite this article

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Abstract

The vast increase in Alzheimer disease (AD) worldwide has grave implications for individuals, family support systems and the health-care systems that will attempt to cope with the disease. Early markers of the disease are essential for efficient selection of clinical trial participants for drug development and for timely treatment once an intervention becomes available. There is avid interest in noninvasive, inexpensive markers that have the potential to identify prodromal AD. This Review considers sensory impairments that have the potential to serve as early indicators of AD, with a focus on olfaction, hearing and vision. Current evidence regarding the potential markers of AD in each modality is examined, with a particular emphasis on olfaction and current findings that olfactory function is associated with prodromal AD. Research suggests that olfactory impairment is associated with other markers that signal the emergence of prodromal AD. Auditory impairment is associated with dementia in epidemiological studies and visual system deficits have been reported in AD; however, the emergence of these deficits in prodromal AD is unclear. Further research is necessary to address the relative sensitivity and specificity of olfactory, auditory and visual measures for the detection of prodromal AD.

Key points

  • Brain areas involved in olfactory processing — such as the olfactory bulb and entorhinal cortex — show very early neuropathology in Alzheimer disease (AD), suggesting that olfactory function is a potential biomarker.

  • Odour memory and odour identification are profoundly affected in individuals with AD and in those at risk of AD, suggesting that several measures of olfactory function signal preclinical AD.

  • Olfaction currently shows the greatest promise of all sensory biomarkers of AD; odour identification impairment predicts conversion to mild cognitive impairment (MCI) in cognitively normal individuals and conversion to AD in patients with amnestic MCI, and shows substantial relationships with other biomarkers of AD.

  • Epidemiological research indicates that hearing loss at baseline is associated with cognitive impairment and incident dementia over a 10-year period.

  • Visual changes in prodromal and clinical AD include retinal thinning in AD, impaired contrast sensitivity in AD and mild MCI, and abnormal pupillary responses that reflect cognitive load in AD and amnestic MCI.

  • Numerous sensory measures in olfaction, hearing and vision are emerging as potential markers of AD; further research is necessary to determine their relationship to other biomarkers and to assess their sensitivity and specificity for early prediction of AD.

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Fig. 1: Regions crucial to olfactory processing.
Fig. 2: Olfactory processing areas affected in Alzheimer disease.
Fig. 3: Braak staging of neurofibrillary changes in prodromal and clinical Alzheimer disease.
Fig. 4: Effect of APOE status on brain activation during odour recognition.
Fig. 5: Potential mechanism of olfactory impairment in Alzheimer disease.
Fig. 6: Proposed emergence of olfactory functional impairment in Alzheimer disease pathological progression.

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Acknowledgements

The author is supported by NIH grant R01AG004085-26 from the National Institute on Aging. The author gratefully acknowledges C. Frank, A. Jacobson, M. Boquet, E. Farley and J. Liu for research assistance, and the patients and staff of the UCSD ADRC, particularly D. Salmon and D. Galasko and the late L. Thal and R. Katzman.

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  1. Department of Psychology, San Diego State University, San Diego, CA, USA

    Claire Murphy

  2. Department of Psychiatry, University of California, San Diego, CA, USA

    Claire Murphy

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Correspondence to Claire Murphy.

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Murphy, C. Olfactory and other sensory impairments in Alzheimer disease. Nat Rev Neurol 15, 11–24 (2019). https://doi.org/10.1038/s41582-018-0097-5

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