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.
"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 . Unaffected siblings of affected cotwins are a powerful way to investigate the temporal relationship between clinical PD and pre-motor symptoms , 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. "
[Show abstract][Hide abstract] ABSTRACT: Questions about the progression of Parkinson’s disease (PD) encompass the beginning of the disease (with what symptoms does it begin), and the subsequent evolution (in what order and how fast the disease progresses). This paper discusses these issues from three points of view: (1) Recent advances (i.e. what have we recently know), (2) knowledge gaps (i.e. what we know/we don’t know – but should) and (3) bridging knowledge gaps (i.e. how will we know).To understand how PD begins we need to observe individuals from the very beginning of the disease, which means assembling a group of individuals before the onset of any PD-associated symptoms. Cohorts can be established to study the very beginnings of PD that are population-based or, perhaps in the future, that are enriched in risk for PD based on genetic risk factors yet to be determined. After onset PD has a heterogeneous course. A number of studies have attempted to understand which symptoms tend to coexist and also to determine clinical subtypes of PD. The value of this ‘subtyping’ may be to prognosticate, if certain types have relatively slower progression of disease, or to define types of PD that have a different pathogenesis and therefore may be amenable to different treatments. To date, however, they have had a cross-sectional rather than longitudinal focus. To understand patterns of progression we must find ways in which to describe patterns of disease progression. These methods can then be applied to studies of etiology and risk factors for PD. If subtypes have distinct determinants then considering PD as a unitary entity by combining subtypes together in analyses risks missing these associations.
"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. "
[Show abstract][Hide abstract] 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
"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. "
[Show abstract][Hide abstract] ABSTRACT: The authors tested the hypothesis that difficulty in identifying odors, a common finding in Parkinson's disease, is associated with more rapid progression of parkinsonian signs in 743 community-dwelling older people without dementia or Parkinson's disease at study onset. Odor identification ability was assessed at baseline with the 12-item Brief Smell Identification Test (mean = 9.0 correct, SD = 2.1), and parkinsonism was assessed annually for up to 5 years with a modified version of the Unified Parkinson's Disease Rating Scale. In an analysis adjusted for age, sex, and education, lower odor identification score was related to higher level of global parkinsonism at baseline (p < .001) and more rapid progression of global parkinsonism on follow-up (p = .002). This result mainly reflected an association of odor identification with worsening parkinsonian gait. The results suggest that impaired odor identification is associated with more rapid progression of parkinsonism in old age, particularly parkinsonian gait disturbance.
Experimental Aging Research 06/2008; 34(3):173-87. DOI:10.1080/03610730802070001 · 0.92 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.