Olfactory Function in Parkinson’s Disease
actually preceded their diagnosis of PD. This is in a line with a number of other studies that could show evidence of olfactory dysfunction in untreated, newly diagnosed patients.5,14
Recent studies support the
view that deficits in sense of smell may precede clinical motor symptoms by years. A study by Ponsen et al.15
on 361 asymptomatic
relatives of PD patients selected 40 relatives with the lowest olfactory performance. Within two years of follow-up, 10% of these first-degree relatives of PD patients with significant olfactory loss developed clinical PD. In a follow-up study five years from baseline testing,16
five relatives
had developed clinical PD as defined by the United Kingdom Parkinson’s Disease Society Brain Bank Diagnostic Criteria for Parkinson’s Disease. Initial clinical (motor) symptoms appeared zero to 52 months (median 15 months) after baseline testing. Poorer performance on each of three olfactory processing tasks was associated with an increased risk of developing PD within five years. Among the olfactory tests used, odour-discrimination testing appeared to be the best predictor of the future development of PD.
In 2007,17 we published data on a clinical follow-up of a previous
in 30 patients diagnosed with idiopathic olfactory loss. Four years from baseline, 7% (n=2) of the individuals with idiopathic olfactory loss who were available for follow-up examination (n=24) had newly developed clinical PD symptoms. Altogether, 13% (n=4) of the patients presented with PD-relevant abnormalities of the motor system. The results indicated that unexplained olfactory loss may be associated with an increased risk of developing PD relevant motor symptoms.
investigation18 By contrast, authors of a twin study19 concluded that smell
identification ability may not be a sensitive indicator of future PD, even in a theoretically at-risk population. This was based on the fact that patients who subsequently developed PD had no evidence of significant smell loss when they were initially tested. However, as pointed out by the authors themselves, the reason for this negative finding might lie in the very long delay of seven years between baseline assessment and follow-up visit. The initial test may have been too early for their subjects to have developed signs of smell dysfunction.
This is in accord with the results of a large longitudinal study by Ross and colleagues,20
who assessed olfactory function in 2,267 elderly men in the Honolulu Heart Program and found an association between smell loss and future development of PD. They came to the conclusion that impaired olfaction can pre-date PD by at least four years and may be a useful screening tool to detect those at high risk of development of PD in later life. This relationship appears to weaken beyond the four-year period. However, currently no accurate information is available on the initial onset of olfactory deterioration. Estimates for the duration of the prodromal phase range from two to 50 years depending on the methods of measurement.21
Recent data on olfactory loss as a PD symptom that is present in the earliest stages of the disease are compatible with predictions made on the basis of neuropathological investigations. Braak et al.22 describe involvement of olfactory pathways and lower brainstem before nigrostriatal pathways are affected, which might cause early non-motor symptoms. Huisman et al.23
found an increase of
(inhibitory) dopaminergic neurons in the olfactory bulb in PD patients. They interpreted their finding within the context of a possible compensatory mechanism in response to the loss of dopaminergic
EUROPEAN NEUROLOGICAL REVIEW 15 Level of functional anosmia 15 Level of functional anosmia 30
Level of normosmia as defined in subjects 18–35 years of age
Figure 1: Olfactory Function in Parkinson’s Disease 45
0
30 40 50 60 Age (years)
Olfactory function of a total of 400 Parkinson’s disease (PD) patients. Results are shown as a composite TDI score (sum of odour threshold, odour discrimination and odour identification score) adjusted to age-independent criteria of hyposmia (olfactory function in a group of 18–35-year-old healthy subjects, considered to be the standard population in terms of normal olfactory sensitivity).6
Figure 2: Olfactory Function in Parkinson’s Disease Adjusted to Age-related Norms
45
70 80 90
30
0
30 40 50 60 Age (years)
Age-related level of normosmia Women
Men
Olfactory function of a total of 400 Parkinson’s disease (PD) patients. Results are shown as a composite TDI score (sum of odour threshold, odour discrimination and odour identification score) adjusted to age-related norms.6
neurons in the basal ganglia. However, in 2008 they described gender-related differences in increase of dopaminergic neurones with a significantly lower number of tyrosine hydroxylase positive cells in control females compared with control males.24
As the
number of dopaminergic cells in the olfactory bulbs of both female and male PD patients equals that of healthy males, the authors came to the conclusion that olfactory dysfunction in PD cannot simply be ascribed to dopamine in the olfactory bulb.
In summary, although the number of prospective studies in this field is still rather small, olfactory loss should be considered a promising contribution to the early diagnosis of PD.
Olfactory Dysfunction in Differential Diagnosis Numerous studies suggest that olfactory disturbances in PD may have diagnostic utility for the differentiation of PD from other movement disorders. Wenning et al.25
presented data suggesting that olfactory
function is differentially impaired in distinct parkinsonian syndromes (PS). They reported a preserved or mildly impaired olfactory function
27
70 80 90
TDI score
TDI score
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