Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

INTRODUCTION
disease, especially in younger patients, but become a common complication of
advanced PD.
Progression of motor symptoms
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The motor features of tremor and bradykinesia are usually localized to the upper
extremities (Uitti et al. 2005). Within one to three years, they extend to the other
ipsilateral limb and affect the contralateral limbs in three to eight years (Poewe and
Wenning 1998). Despite the fact that PD is almost always a bilateral disease, this
asymmetrical pattern remains so throughout most of the course of the illness, even in
advances stages (Hughes et al. 2001). As tremor gravity is rather stable over time,
whereas severity of bradykinesia and rigidity evolve similarly, some authors
hypothesized the existence of different underlying pathophysiological processes (Louis
et al. 1999).
Non-motor symptoms
Although motor features define PD, various non-motor symptoms, equally
significant and potentially disabling, are typically seen. They include autonomic
dysfunction (including orthostatic hypotension, bowel and bladder difficulties,
abdominal bloating, constipation, urinary urgency and dysfunction, flushing, excessive
sweating, temperature dysregulation, and impotence/sexual dysfunction; Jost 2003,
Poewe 2008), sensory symptoms (eg. pain, paresthesiae; Quinn et al. 1986), sleep
disturbances (REM sleep behaviour disorder, periodic limb movements, etc.; Stacy
2002), psychiatric changes (depression, hallucinations, anxiety symptoms), and
cognitive dysfunction (memory deficits, bradyphrenia, executive function difficulty,
dementia; Levin and Katzen 2005, Rippon and Marder 2005, Caviness et al. 2007).
Depression is common in PD, as it develops in about 50% of individuals with PD
(McDonald et al. 2003). Dementia is significantly more frequent in PD, especially in
older patients, ranging from 40-80% of patients (Cedarbaum and McDowell 1987, Emre
2003, Poewe 2008). Non-motor symptoms, present with considerable variability, may