Olfactory dysfunction is among the earliest nonmotor features of Parkinson disease (PD). Such dysfunction is present in approximately 90% of early-stage PD cases and can precede the onset of motor symptoms by years. The mechanisms responsible for olfactory dysfunction are currently unknown. As equivalent deficits are observed in Alzheimer disease, Down syndrome, and the Parkinson-dementia complex of Guam, a common pathological substrate may be involved. Given that olfactory loss occurs to a lesser extent or is absent in disorders such as multiple system atrophy, corticobasal degeneration, and progressive supranuclear palsy, olfactory testing can be useful in differential diagnosis. The olfactory dysfunction in PD and a number of related diseases with smell loss correlates with decreased numbers of neurons in structures such as the locus coeruleus, the raphe nuclei, and the nucleus basalis of Meynart. These neuroanatomical findings, together with evidence for involvement of the autonomic nervous system in numerous PD-related symptoms, suggest that deficits in cholinergic, noradrenergic and serotonergic function may contribute to the olfactory loss. This Review discusses the current understanding of olfactory dysfunction in PD, including factors that may be related to its cause. Doty, R. L. Nat. Rev. Neurol. 8, 329-339 (2012); published online 15 May 2012; doi:10.1038/nrneurol.2012.80
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Corporal Michael J Crescenz VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA
Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USACorporal Michael J Crescenz VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA
Fullard, Michelle E.
Morley, James F.
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Corporal Michael J Crescenz VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA
Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USACorporal Michael J Crescenz VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA
Morley, James F.
Duda, John E.
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Corporal Michael J Crescenz VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA
Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USACorporal Michael J Crescenz VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA
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Univ Nebraska, Dept Biol, Omaha, NE 68182 USAUniv Nebraska, Dept Biol, Omaha, NE 68182 USA
Chase, Bruce A.
Markopoulou, Katerina
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NorthShore Univ HealthSyst, Dept Neurol, Evanston, IL USA
Univ Chicago, Dept Neurol, Chicago, IL 60637 USAUniv Nebraska, Dept Biol, Omaha, NE 68182 USA
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Univ Michigan, Dept Radiol, Funct Neuroimaging Cognit & Mobil Lab, Div Nucl Med, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
VAAAHS, Neurol Serv, Ann Arbor, MI 48105 USA
VAAAHS, GRECC, Ann Arbor, MI 48105 USAUniv Michigan, Dept Radiol, Funct Neuroimaging Cognit & Mobil Lab, Div Nucl Med, Ann Arbor, MI 48109 USA
Bohnen, Nicolaas I.
Mueller, Martijn L. T. M.
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Mueller, Martijn L. T. M.
Kotagal, Vikas
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USAUniv Michigan, Dept Radiol, Funct Neuroimaging Cognit & Mobil Lab, Div Nucl Med, Ann Arbor, MI 48109 USA
Kotagal, Vikas
Koeppe, Robert A.
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Koeppe, Robert A.
Kilbourn, Michael A.
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Kilbourn, Michael A.
Albin, Roger L.
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA
VAAAHS, Neurol Serv, Ann Arbor, MI 48105 USA
VAAAHS, GRECC, Ann Arbor, MI 48105 USAUniv Michigan, Dept Radiol, Funct Neuroimaging Cognit & Mobil Lab, Div Nucl Med, Ann Arbor, MI 48109 USA
Albin, Roger L.
Frey, Kirk A.
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Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USAUniv Michigan, Dept Radiol, Funct Neuroimaging Cognit & Mobil Lab, Div Nucl Med, Ann Arbor, MI 48109 USA
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Univ Michigan, Dept Radiol, Ann Arbor, MI 48105 USA
Univ Michigan, Dept Neurol, Ann Arbor, MI 48105 USA
Dept Vet Affairs, Neurol Serv, Ann Arbor, MI USA
Dept Vet Affairs, GRECC, Ann Arbor, MI USA
Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Radiol, Ann Arbor, MI 48105 USA
Univ Michigan, Funct Neuroimaging Cognit & Mobil Lab, Dept Neurol, Ann Arbor, MI 48105 USAUniv Michigan, Dept Radiol, Ann Arbor, MI 48105 USA
Bohnen, Nicolaas I.
Mueller, Martijn L. T. M.
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Univ Michigan, Dept Radiol, Ann Arbor, MI 48105 USAUniv Michigan, Dept Radiol, Ann Arbor, MI 48105 USA
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Univ Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USAUniv Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
Sharer, James D.
Leon-Sarmiento, Fidias E.
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Univ Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USAUniv Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
Leon-Sarmiento, Fidias E.
Morley, James F.
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Philadelphia Vet Adm Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA
Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USAUniv Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
Morley, James F.
Weintraub, Daniel
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Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USAUniv Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA
Weintraub, Daniel
Doty, Richard L.
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Univ Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USAUniv Penn, Ctr Smell & Taste, Dept Otorhinolaryngol Head & Neck Surg, Perelman Sch Med, Philadelphia, PA 19104 USA