Idiopathic hyposmia as a preclinical sign of Parkinson's disease

Abstract

Olfactory dysfunction is an early and common symptom in Parkinson's disease (PD). In an effort to determine whether otherwise unexplained (idiopathic) olfactory dysfunction is associated with an increased risk of developing PD, we designed a prospective study in a cohort of 361 asymptomatic relatives (parents, siblings, or children) of PD patients. A combination of olfactory detection, identification, and discrimination tasks was used to select groups of hyposmic (n ‫؍‬ 40) and normosmic (n ‫؍‬ 38) individuals for a 2-year clinical follow-up evaluation and sequential single-photon emission computed tomography (SPECT), using [123 I]␤-CIT as a dopamine transporter ligand, to assess nigrostriatal dopaminergic function at baseline and 2 years from baseline. A validated questionnaire, sensitive to the presence of parkinsonism, was used in the follow-up of the remaining 283 relatives. Two years from baseline, 10% of the individuals with idiopathic hyposmia, who also had strongly reduced [123 I]␤-CIT binding at baseline, had developed clinical PD as opposed to none of the other relatives in the cohort. In the remaining nonparkinsonian hyposmic relatives, the average rate of decline in dopamine transporter binding was significantly higher than in the normosmic relatives. These results indicate that idiopathic olfactory dysfunction is associated with an increased risk of developing PD of at least 10%.

Epidemiology and etiology of Parkinson’s disease: a review of the evidence

“…At two years of follow-up, four of 40 relatives with hyposmia had PD, versus none of 38 relatives without hyposmia [516]. At five years of follow-up, one additional relative with hyposmia had PD [517].…”

Parkinson's Disease Therapeutics: New Developments and Challenges Since the Introduction of Levodopa

“…A number of studies have provided evidence that PD patients commonly report a loss of their sense of smell prior to the development of motor PD symptoms (Doty et al, 1988;Tissingh et al, 2001;Muller et al, 2002a, b;Ponsen et al, 2004;Sommer et al, 2004). The results of a recent longitudinal study in 2267 elderly men in the Honolulu Heart Study demonstrate that loss of olfaction can precede PD motor symptoms by at least 4 years, thereby suggesting that it could serve as a screening tool to predict the future development of PD (Ross et al, 2008).…”

FDG PET, dopamine transporter SPECT, and olfaction: Combining biomarkers in REM sleep behavior disorder

“…Loss of striatal dopamine transporter (DAT) binding on single photon emission computed tomography (DAT‐SPECT) indicates imminent phenoconversion 14, 15. In addition, RBD subjects with baseline hyposmia have a high risk of developing PD/DLB within 5 years of follow‐up 16, 17…”