Las fuentes morales

This chapter will address the link between the sense of smell (as measured by UPSIT 40) and the typical characteristics and demographic features of the study group, including UPSIT 40 sense of smell scores, gender, age,

smoking history, taste reported, disease duration and cognitive function in each sense of smell sub-group. All these demographic features were chosen as they may contribute to loss of sense of smell seen in PD patients.

3.1.1. Parkinson’s Disease and Sense of Smell

There is now good research evidence that the ability to smell is significantly affected in PD compared to the general population (Casjens et al 2013, Litvan et al 2003, Ramaker et al 2002, Hawkes et al 1999, Hawkes and Shephard 1998, Mesholam et al 1998, Hawkes et al 1997, Doty et al 1988, Quinn et al 1987), with at least 80% of PD patients affected (Double et al 2003, Mesholam et al 1998, Hawkes et al 1997) (see section 1.2.1.2.). There is also evidence that impaired olfaction may precede the classical motor manifestations of PD by several years (Ross et al 2008, Haehner et al 2007, Stiasny-Kolster et al 2005, Ponsen et al 2004, Hawkes 2003, Berendse et al 2001, Doty et al 1988) (see section 1.2.1.2), suggesting that neuronal

damage occurs early in the diagnosis, even before the classical motor signs are evident (Braak et al 2003) (see section 8.1 figure 8.2). Interest in the loss of sense of smell (seen in PD patients) has grown markedly in the past few years, driven by the hope of developing neuroprotection treatment for PD patients in the early stage of the disorder. Therefore, one of the aims of this chapter is to study the pattern of distribution of mild/moderate microsmia, severe microsmia and anosmia in PD patients selected for this PhD study.

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3.1.2. Gender and Sense of Smell

In general, females have a better sense of smell than males (Liu et al 1995). This observation has been made by numerous investigators, using

psychophysical, electrophysical and imaging techniques (Lundstrom et al 2006, Dalton et al 2002, Brand and Millot 2001, Cain 1982). The discussion as to why these effects should occur is inconclusive. So far, the increased olfactory sensitivity in females has been speculated to be attributed to numerous factors including hormonal effects (Doty 1986), verbal skills (Larsson et al 2004) or congenital factors (Schaal et al 2004). This agrees with normative data for the UPSIT-40 in the United States, showing

considerable influence of gender (Doty 1995). This was also supported by the Silveria-Moriyama et al (2008) study which found that gender was an independent predictor of the UPSIT-40 score. The UPSIT-40 has therefore adjusted for this and both female and male percentile scores can be seen in appendix 4. Therefore, one of the objectives of this chapter is to confirm or refute whether females in this PD study group do -in fact- have a better sense of smell compared to males.

3.1.3. Ageing and Sense of Smell

As previously mentioned (in section 1.2.3.) ageing is among the factors that put an individual at risk of developing olfactory dysfunction (Hawkes 2008, Doty 1995, Doty et al 1984). However, it is also known it is unlikely that the PD olfactory defect is simply due to ageing (Hawkes 2008). Therefore, one of the objectives of this chapter is to confirm or refute whether ageing does have an impact on loss of sense of smell in PD and to what degree.

3.1.4. Smoking and Sense of Smell

Little is known about the effect of cigarette smoking on the ability to smell. Previous studies on this topic have led to inconsistent findings. For example, Frye et al (1990) found that smoking causes long-term but reversible adverse effect on the ability to smell. This was not replicated by Ishimaru and Fujii

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(2007) research who found that although smoking reduces the sense of smell function, recovery of sense of smell after cessation of smoking appears to be exceptional. Katotomichelakis et al. 2007, in their study found smoking to be adversely associated with the olfactory ability in a dose-related manner and that smokers were found to be nearly six times as likely to have evidence of an olfactory deficit as non-smokers. This was supported by Vennemann et al (2008). However, a study by Lucassen et al (2014) showed that a history of smoking was associated with better olfaction among PD. Lucassen et al (2014) conclude that although the interaction between smoke and the

olfactory system at a peripheral level is a very intriguing hypothesis, it is also possible that cigarette smoke may protect olfactory structures within the brain. This is supported by the fact that more than 60 epidemiological studies are consistent in reporting that smokers have a lower risk for

developing PD (Li et al 2015, Burton et al 2013, Hawkes et al 2007, Hawkes et al 2009, Allam et al 2004). However, the mechanism(s) by which cigarette smoking may confer a protective effect in PD is unknown and warrants

further study.

3.1.5. Taste and Sense of Smell

Since brain stem regions associated with early Parkinson's disease (PD) pathology encroach upon those involved in taste function (caudal

orbitofrontal cortex and immediately adjacent agranular insula) (Welge- Lussen et al 2005, De Araujo et al 2003), the ability to taste may be

compromised in PD (Doty et al 2015). However, studies regarding the link between taste and sense of smell generally have been contradictory. Sienkiewicz-Jarosz et al (2005) report in their study that taste is unaffected by PD, Shah et al (2008) suggest that up to 28% of patients with established disease also have taste problems but Deems et al (1991) in their early

research reported that 87% of those who report a taste problem -in fact- have no measurable taste deficit (false-positive rate).

Although it is suggested there can be a central cause of taste loss, Hawkes and Doty (2009) suggest this appears to be due to retro nasal olfaction as

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odorants released from food escapes into the retropharyngeal space. Therefore, it appears any food entering the mouth will evoke a sensation of both taste and smell, unless it is pure odourless tastant evoking solely sweet, sour, salt, bitter or savoury taste qualities.

Overall, at this present time, it appears the coexistence of taste impairment with PD is not typical of PD (Sienkiewicz-Jarosz et al 2005) and Fernando et al (2005) suggest if it does occur at all it is probably a late feature of PD.

3.1.6. Disease Duration and Sense of Smell

The question of whether olfactory deficits in PD are related or unrelated to factors such as disease duration has been of considerable debate over the last 40 years. Some researchers report no associations (Haehner et al 2009, Hawkes et al 1997, Doty et al 1992, Doty et al 1988, Quinn et al 1987, Ward et al 1983), whilst others note associations (Cavaco et al 2015, Debb et al 2010, Tissingh et al 2001, Stern et al 1994, Ansari and Johnson 1975). These inconsistent findings may be related to procedural differences in measuring olfactory dysfunction (e.g., use of different assessment instruments, different methods used in the interpretation of olfactory

performance (see table 1.1 and 1.2 section 1.2.1.). However, interestingly, odour discrimination performance (in patients with PD) improves concurrently with clinical motor improvement after stereotactic neurosurgical treatment using deep brain stimulation (Hummel et al 2005). This possibly indicates that at least some aspects of olfactory dysfunction in PD may be secondary to on-going degenerative processes in PD.

However, none of the above studies have divided patients according to their severity of smell loss and disease duration. This section will address this by, firstly examining the whole group and then dividing the duration of disease into 5-year intervals. The PD patients will then be analysed according to their degree of smell loss (mild/moderate microsmia, severe microsmia or

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3.1.7. Cognitive Function and Sense of Smell

Odour identification has been linked in some studies to language, verbal memory, and processing speed in healthy elderly (Westervelt et al 2005, Swan and Carmelli 2002). Whilst in other studies, this has not been

proposed (Hawkes et al 1997, Doty et al 1989, Quinn et al 1987). However, this link between cognitive impairment and olfactory loss remains poorly explored in PD, although, Postuma and Gagnon (2010) recently reported significant correlations between verbal and nonverbal memory and olfactory loss in PD. Furthermore, Bohnen et al (2010) found a positive correlation between odour identification scores and verbal memory in patients with PD who have olfactory loss. Bohnen et al (2010) implicated limbic cholinergic denervation and suggests that this cholinergic denervation may be more pronounced in a subset of PD patients with early emerging cognitive deficits and that greater deficits in odour identification may identify patients at risk of clinically significant cognitive impairment (Bohnen et al 2010, Bohnen and Albin 2010).

Part of this chapter aims to confirm or refute whether cognition has an impact on sense of smell in this PD patient study group.