Alzheimer's Disease and Parkinson's Disease - Essay Example

To Compare and Contrast: Alzheimer’s disease and Parkinson’s disease Alzheimer’s disease and Parkinson’s disease are common neurodegenerative disorders with no treatments available so far. In fact, Alzheimer’s disease is the most common neurodegenerative disorder with Parkinson’s being the second. Both are idiopathic disorders with their pathogenesis not known much. However, human genome projects reveal that some variants of both these diseases do have inheritable components. Clinically, both of them present in older persons, usually above 65 years and the symptoms only worsen as age increases. Dementia is an important component in Alzheimer’s disease while Parkinson’s disease includes a wide range of motor-system disorders. Both Parkinson’s (PD) and Alzheimer’s (AD) diseases are common neurodegenerative disorders (Beal, 2005). While the prevalence of AD increases with age, there is not much increase in case of PD. AD has a prevalence of about 1% among those between 65 to 69 years of age (Hy & Keller, 2000) while PD has a prevalence of 0.5 to 1% in this age group (Nussbaum & Ellis, 2003). However, the prevalence of AD is 40 to 50% among those 95 years of age and over (Hy & Keller, 2000) and that of PD is only 3% in those 80 years of age and older (Nussbaum & Ellis, 2003). Both these conditions result due to loss of neurons in parts of brain. AD particularly affects neurons in the cortex and the hippocampus (Mc Khann, Drachman, Folstein, Katzman, Price & Stadlan, 2003) while PD affects neurons in the substantia nigra (Nussbaum & Ellis, 2003). AD presents mainly with progressive impairment in memory. There is impairment of judgement, decision making, concentration, orientation and language. The patient can present with agitation, psychosis, depression, apathy, disinhibition, anxiety, delusions, purposeless behavior, and disorders of sleep and appetite (Cummings & Back, 1998). Of all these, agitation is the most common symptom and psychosis is seen in 30-60% of the patients. The most common behavioural changes are personality alterations (Cumming & Back, 1998). The destruction of cholinergic neurons in the basal forebrain and the resulting deficit in central cholinergic transmission is the cause for characteristic cognitive and non-cognitive symptoms in AD (Cummings & Back, 1998). Another theory as far as the cause of symptoms in AD is concerned is Glutamate excitotoxicity. Excessive activation of NMDA receptors by glutamate is said to cause neuronal death in Alzheimers disease due to increases in intracellular Ca2+ (Bleich, Romer, Wiltfang & Kornhuber, 2003). PD mainly presents with symptoms of motor system. It is characterized by resting tremor, bradykinesia, rigidity and postural instability (Nussbaum & Ellis, 2003). The tremors can be seen in the hands, arms, legs, jaw and face. Rigidity affects the limbs and the trunk. These symptoms worsen as days go by and the patients will develop difficulty in walking, talking, eating, brushing and other day-to-day activities. They also develop difficulty in coordination and balance. In both the conditions, diagnosis is made clinically by neurologic examination and by excluding other similar clinical conditions. The other causes of dementia which need to be excluded before arriving at the diagnosis of AD are vascular causes of dementia and other neurodegenerative diseases such as Picks disease and diffuse Lewy-body dementia (Martin, 1999). In the case of PD, this condition needs to be differentiated from Parkinson’s signs arising as a consequence of drugs, encephalitis or vascular insults (Nussbaum & Ellis, 2003). The pathological diagnosis in both the conditions can be obtained mainly at autopsy (Nussbaum & Ellis, 2003). The pathological findings that are commonly seen in case of AD are neuronal loss, extracellular senile plaques containing beta-amyloid, and neurofibrillary tangles composed of hyperphosphorylated microtubular protein tau (Nussbaun & Ellis, 2003). The senile plaques and neurofibrillary tangles accumulate within the grey matter of the cerebral cortex and cerebral nerve cells. These compress and destroy the nerve fibers leading to clinical symptoms. The plaques and fibers can also aggregate around blood vessels causing structural weakening of the vessels, intracerebral hemorrhage and stroke. The hallmark of PD in pathology specimens is dopaminergic neuronal loss and presence of intraneuronal inclusion bodies called Lewy bodies in substantia nigra. The positron emission tomography with flurodopa F-18 can reveal abnormal striatial uptake in the brain even before clinical symptoms are apparent (Nussbaun & Ellis, 2003). Neuronal loss can also be seen in locus ceruleus, dorsal motor nucleus of the vagus, raphe nuclei, and nucleus basalis; and Lewy bodies can be detected in these areas also (Mackenzie, 2001). These Lewy bodies consist mainly of alpha-synuclein. They may also be detected extracellular following death of the cells which initially harboured them. Other features seen during pathological examination are astrogliosis, microglial cell activation and pigmented macrophages. It has been estimated that at least 50% of the neuronal cells must undergo degeneration to produce clinical symptoms (Mackenzie, 2001). However, sometimes, even in AD, Lewy bodies can be detected (Mackenzie, 2001). The neurochemical alterations that occur in AD are deficits in acetylcholine, norepinephrine, and serotonin; of these, acetylcholine is the most affected (Cummings & Back, 1998) while the alterations in PD are deficits of dopamine. AD and PD are different as far as neurochemical alterations in brain are concerned. The etiology of these diseases is idiopathic. There are variants to the normal pattern of diseases in both which have some relation to inheritance. In case of AD, about 6 to 7 % of patients have the onset at an age less than 61 years. Of these, about 7% are familial with autosomal dominant pattern of inheritance and high penetrance (Nussbaun & Ellis, 2003). The genetic inheritance is due to the mutations of the gene coding for the beta amyloid precursor which is present on chromosome 21 (Nussbaun & Ellis, 2003). Other genes which are involved in genetic inheritance of AD are presenilin-1 on chromosome 14, presenilin 2 on chromosome 1 and variant of APOE gene, the one which codes for apolipoprotein E (Nussbaun & Ellis, 2003). Though most of the cases of PD are said to be sporadic, it has been observed that monozygotic twins with an onset of disease before the age of 50 years do have a very high rate of concordance which is much higher than that of dizygotic twins with early-onset disease (Nussbaun & Ellis, 2003). Furthermore, studies have also shown an increased risk of the disease among first- degree relatives of the patients (Nussbaun & Ellis, 2003). The inheritance can be autosomal dominant or autosomal recessive. Mutations in the gene coding for alpha synuclein are said to be autosomal dominant (Nussbaun & Ellis, 2003) and there is accumulation of this protein as a result of mutations. These mutations are Ala53Thr and Ala30Pro. The autosomal recessive form has an early onset of disease, before the age of 40 years and is known as autosomal recessive juvenile parkinsonism. It is a rare form of PD. The genetic mutation has been mapped to 6q25–27 which is gene coding for a protein termed parkin (Nussbaun & Ellis, 2003). In this case, it is the loss of the protein parkin that leads to accumulation of ubiquitin that causes the pathology (Liu et al., 2007). Thus, it can be said that both AD and PD have idiopathic etiology. In cases of early onset of diseases in both, there seems to be a genetic factor involved. There have been various reports about the possibility of common origins of AD and PD. This is because evidence shows that one-fourth of AD patients develop Parkinsonian symptoms, and that patients with rapidly progressing PD have more than an eightfold increased risk of developing AD when compared to patients with slowly progressing PD (Treichel, 2004). However, a study by Levy and others (2004) has disproved this hypothesis. Therefre it can be said that AD and PD do not have common origins. As far as treatment is concerned, in both AD and PD, currently available medications can only produce moderate symptomatic benefits but cannot stop disease progression. The drugs which are used to control symptoms in AD are acetylcholinesterase (AchE) inhibitors for mild to moderate cases, and memantine, an NMDA (N-methyl-D-aspatarte)-receptor antagonist for moderate to severe cases (Klafki, Staufenbiel, Kornhuber & Wiltfang, 2006). The cholinergic hypothesis is the rational basis for the use of AChE inhibitors in Alzheimers disease therapy. Inhibition of acetylcholinesterase leads to an increase in the acetylcholine concentration in the synaptic cleft and enhances cholinergic transmission. The commonly used AChE inhibitors are galantamine, donepezil and rivastigmine. NMDA antagonist memantine acts by non-competitive inhibition of NMDA receptors. It has moderate affinity to these receptors and hence protects neurons while leaving physiological NMDA-receptor activation unaffected (Klafki, Staufenbiel, Kornhuber & Wiltfang, 2006). Mechanism based therapeutic approaches targeting beta-amyloid and tau pathologies are still under research. In case of PD, it is treated with levodopa, dopamine agonists, selegiline, anticholinergics, amantadine and catechol O-methyltransferase (COMT) inhibitors (Conley & Kirchner 1999, MIMS 2007). Levodopa helps to establish brain dopamine and thus produces symptomatic relief (Winstanley 2002, MIMS 2007). However, it itself may cause motor symptoms as side effects after 2 years. Dopamine agonists produce their action by stimulating dopamine receptors and also by causing anti-oxidant effects. The dopamine agonists which are currently used are bromocriptine mesylate, pergolide mesylate, pramipexole, and ropinirole hydrochloride (Conley & Kirchner 1999, MIMS 2007). Selegiline is useful because of its antioxidant properties. It is mainly neuroprotective. It is a selective inhibitor of type B monoamine oxidase. COMT inhibitors are given in conjunction with levodopa. They inhibit the enzyme COMT which degrades levodopa (Conley & Kirchner, 1999). Unlike in AD, there is hope for surgical treatment in PD. Surgery is indicated when medical treatment cannot control symptoms or when side effects from levodopa are intolerable (Conley & Kirchner, 1999). The surgical procedures done in regard to PD are globus pallidus internal segment pallidotomy, deep brain stimulation and fetal nigral transplantation (Coley & Kirchner, 1999). Thus the treatments for AD and PD are different. Both AD and PD are common neurodegenerative disorders with similar age of onset and idiopathic pathogenesis. Variants with earlier onset in both conditions have genetic component involved in pathogenesis. Clinically, AD presents with progressive dementia, behavioral and personality changes, while PD presents with motor system related symptoms. Decreased acetyl choline levels is the cause for clinical manifestations in AD while decreased dopamine levels is the cause in PD. Pathological findings are evident only at autopsy. While neuronal loss is evident in both, the regions involved in AD are cortex and the hippocampus and the region involved in PD is substantia nigra. Pathological findings pathognomonic of AD are senile plaques and neurofibrillary tangles while that in PD is Lewy’s bodies. Treatment in both conditions is mainly medical and that too only to control symptoms and not to prevent progression of disease. There is hope for surgical cure in case of PD in future. References Beal, M.F., Ludolph, A.C., Lang, A.E. (2005). Neurodegenerative diseases: Neurobiology, Pathogenesis and Therapeutics. Cambridge: Cambridge university press. Bleich, S., Romer, K., Wiltfang, J., Kornhuber, J. (2003) Glutamate and the glutamate receptor system: a target for drug action [Electronic version]. Int J Geriatr Psychiatry, 18, S33–40 Cummings, J.L., & Back, C. (1998). The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimers disease [Electronic version]. Am J Geriatr Psychiatry, 6, S64–78. Conley, S.C., & Kirchner, J.T. (1999). Medical and surgical treatment of Parkinson’s disease. Postgraduate Medicine online (peer reviewed) 106(2). Retrieved on September 19, 2007 from http://www.postgradmed.com/issues/1999/08_99/conley2.htm Hy, L.X., & Keller, D.M. (2000). Prevalence of AD among whites: a summary by levels of severity [Electronic version]. Neurology, 55, 198-204.  Klafki, H.W., Staufenbiel, M., Kornhuber, J., & Wiltfang, J. (2006). Therapeutic approaches to Alzheimers disease [Electronic version]. Brain, 129, 2840-2855. Levy,G., Louis, E.D., Santana, H.M., Cote, L., Andrews, H., Harris, J., et al. (2004). 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