Smell identification ability in twin pairs discordant for Parkinson's disease

The Parkinson's Institute, Sunnyvale, California, USA.
Movement Disorders (Impact Factor: 5.68). 06/2005; 20(6):687-93. DOI: 10.1002/mds.20389
Source: PubMed


Olfactory dysfunction has been proposed to be a sign that may precede the motor features of Parkinson's disease (PD). To determine whether smell identification deficits predict subsequent PD, we studied smell identification ability using the University of Pennsylvania Smell Identification Test (UPSIT) in 62 members of male twin pairs discordant for PD at baseline. Smell identification ability was reduced at baseline in the twins with PD compared to their unaffected brothers (23 vs. 31 of 40; P = 0.001). UPSIT scores were not reduced in the twins without PD when compared to age- and gender-specific normal values. After a mean interval of 7.3 years, 28 unaffected twins were still alive and 19 agreed to a second evaluation. Two had newly developed PD. Neither twin had impaired smell identification at baseline. The average decline in UPSIT percentile scores in these 2 twins was greater than in the 17 twins who did not develop PD (-68% vs. -24%; P = 0.01). In subjects who did not meet Core Assessment Program for Intracerebral Transplantations diagnostic criteria for PD at baseline, the presence of cardinal signs of parkinsonism was not associated with lower baseline UPSIT scores nor with a subsequent decline. Smell identification ability may not be a sensitive indicator of future PD 7 or more years before the development of motor signs, even in a theoretically at-risk population.

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    • "Having a first or second degree relative with PD confers only a 2-to 4-fold increase in risk for developing the disorder based on previous case-control studies [6]. Unaffected siblings of affected cotwins are a powerful way to investigate the temporal relationship between clinical PD and pre-motor symptoms [7], however twins are rare and only a few twin cohorts exist. Currently, monogenic forms of PD represent only a small fraction of individuals and are rare, thus it is difficult to gather large numbers of these individuals. "
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    • "In light of such findings, it is tempting to conclude that at least some asymptomatic PARK8 gene carriers are similar to asymptomatic Huntington's disease (HD) gene carriers, who do not exhibit smell loss until sometime near the expression of the clinical phenotype (Bylsma et al., 1997; Moberg and Doty, 1997). It is not yet known as to when the loss appears relative to the onset of motor dysfunction in either HD or PD, although one HD study suggests that the loss may occur 5–10 years before symptom onset (Paulsen et al., 2008).In most sporadic cases ofPD in the United States, this average period is likely less than 10 years, although exceptions are apparent (Marras et al., 2005; Ross et al., 2008; Tanner et al., 2007). The possibility exists that age is associated with gene penetrance, although other factors may be involved as well. "
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    ABSTRACT: Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclein- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances.
    Neurobiology of Disease 12/2011; 46(3):527-52. DOI:10.1016/j.nbd.2011.10.026 · 5.08 Impact Factor
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    • "We are not aware of any prior research relating olfactory function to change in parkinsonism. Difficulty recognizing familiar odors is a well-established feature of Parkinson's disease (Doty et al., 1992; Mesholam et al., 1998), but cross-sectional studies of people with Parkinson's disease (Doty, Deems, & Stellar, 1988; Doty, Ricklan, Deems, Reynolds, & Steller, 1989) or at risk for it (Marras et al., 2005) have not observed an association between odor identification and severity of parkinsonism. These studies were based on fewer than 100 participants, however, possibly limiting power to identify an association. "
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