10

Bioinformatics of the Brain

PD typically affects 5–6 persons out of every 1000 [48, 49]. About 1–2% of

persons over 65 and 4% of adults over 80 are affected [50]. In PD, α-synuclein

proteins accumulate as Lewy bodies in the nervous system. Lewy bodies de-

stroy relevant nerve cells and connections and, stop the exchange of neuro-

transmitters [51]. As a result, signals can no longer be sent over these lines,

and issues arise with activities such as mobility and attention management.

Tremor, bradykinesia, and postural instability thus arise as the distinctive

indicators of this disease [50].

Many different underlying mechanisms have been proposed in the patho-

physiology of PD such as genetic causes, congenital causes, toxic agent expo-

sure, mitochondrial dysfunction, trauma, inflammation, and oxidative stress,

[52]. Outcome of PD is defined by the loss of dopaminergic neurons in the

substantia nigra as well as localization of the Lewy bodies in the midbrain

leading to the gradual loss of movement capacity [53].

Observation of the response to dopamine drugs (dopamine agonists and

L-dopa) is the most widely used diagnostic method, but imaging techniques

such as MRI and tomography fail to diagnose PD [54]. The diagnosis of PD

typically relies on clinical findings and patient history [55]. Laboratory tests

may be sought to exclude other forms of parkinsonism. However, there are

no specific biological markers for antemortem diagnosis of PD. Particularly in

the early stages of the disease, diagnoses made immediately after the onset of

symptoms can change in approximately one-third of patients within the first

five years [56]. The diagnostic accuracy of patients treated for PD based on

clinical assessment is found to be 76% in postmortem studies [57]. However,

under the supervision of a specialist experienced in movement disorders, the

diagnostic specificity of the presence of resting tremor, asymmetric bradyki-

nesia, rigidity, and a good response to L-Dopa is 98%, with a sensitivity of

91%. Final confirmation of the diagnosis based on current clinical features is

often possible through neuropathological examination.

Distinguishing PD from atypical parkinsonisms and other parkinsonian

syndromes is crucial not only for determining treatment response and prog-

nosis but also for selecting appropriate patients for clinical trials, especially

those related to potential neuroprotective therapies. Although various crite-

ria have been proposed for the diagnosis of PD [58], the most used criteria

today are the Clinical Diagnostic Criteria of the United Kingdom Parkinson’s

Disease Society Brain Bank, published in the late 1980s. According to these

criteria, bradykinesia is essential for diagnosis, and the presence of at least one

additional symptom such as rigidity, resting tremor, or postural instability is

required [59]. There are four main symptoms in PD acronymized as TRAP:

Tremor at rest, rigidity, akinesia, and postural instability [55].

Clinical findings in PD are usually asymmetrical, and not all of them may

be found together. Secondary motor symptoms are hypoxemia, dysarthria,

dysphagia, sialorrhea, micrographia, shuffling, festination, freezing, slowing of

activities of daily living, blepharospasm, and dystonia. The first symptoms

are resting tremors in one extremity, clumsiness of the hand especially in