Brain Systems and Cognitive Effects of Parkinson's Disease

Introduction to Parkinson's Disease

Parkinson's disease is a crippling, degenerative disorder that primarily affects a movement center of the brain. The disorder creates a shortage or limiting of the action of the neurotransmitter dopamine, which in a healthy brain triggers purposeful movement in the neurons of the affected region. The disease is also shown to affect norepinephrine to some degree. Parkinson's disease is usually progressive, beginning with a single-sided tremor, typically in one hand and particularly when the individual is at rest. It can then progress to tremors in all the limbs, bradykinesia (slow movement), akinesia (an inability to move), rigid limbs, a shuffling gait, and a stooped posture. It is also not uncommon for people with the disease to have reduced facial expressions and to speak in a soft voice as a result of the neurological effects. Individuals may also experience fatigue, depression, personality changes, dementia, and other cognitive function impairments (National Institute of Neurological Disorders and Stroke, 2010).

There is some difficulty in separating the severe functional limitations of the disease and its bleak prognosis from cognitive changes such as clinical depression, as the disorder has limited treatment options and can seriously affect quality of life. It is also clear that knowledge of neurotransmitters and the normal function of receptors and transmitters — both in the healthy brain and in the Parkinson's-affected brain — remains incomplete. Cognitive manifestations, especially dementia, can be positively linked to the disorder itself rather than to a normative cognitive response to decreased quality of life, and are also shown to directly affect the level of disability associated with the disease (Weintraub, Moberg, Duda, Katz & Stern, 2004, pp. 784–788).

According to the National Institute of Neurological Disorders and Stroke:

Primary Symptoms and Early Cognitive Changes

The four primary symptoms of PD are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. PD usually affects people over the age of 50. Early symptoms of PD are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of PD patients, may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions. (NINDS, 2010)

There is a longstanding tradition of research into the subtle cognitive changes in individuals, even in early-onset untreated Parkinson's disease. This research has been ongoing since the 1980s and provides a great deal of insight into the normal functioning of the brain centers affected by the disease. An early study found:

No impairment of general intellectual function was found in the patients using the WAIS and New Adult Reading IQ tests and no abnormalities were apparent on cognitive estimates and two-choice Recognition Memory Tests. Patients with Parkinson's disease, however, had significantly greater difficulty in shifting conceptual sets and produced more perseverative errors on both the modified Wisconsin Card Sorting Test and Benton's Word Fluency Test. These subtle cognitive difficulties might underlie the mental inflexibility and rigidity of Parkinson's disease and could be attributed to destruction of the ascending dopaminergic meso-corticolimbic pathway. (Lees & Smith, 1983, p. 257)

Other early work attempted to identify the manner in which medical interventions slowed or altered the cognitive effects of the disease, likely in the hope that early intervention would ultimately limit, reduce, or even eliminate cognitive impairments, as it sometimes did with the motor effects (Taylor, Saint-Cyr & Lang, 1987, pp. 35–51). Ultimately, most research pointed to the conclusion that cognitive impairment, though often subtle through the early stages of the disease, was persistent and often progressive, with the level of impairment remaining largely independent of pharmacological intervention (Gotham, Brown & Marsden, 1988, pp. 299–321).

Dementia in Parkinson's Disease: Chemical vs. Structural Causes

It was made clear early on that, despite initial assumptions, the type of disease process that caused the rare but persistent outcome of dementia in Parkinson's patients — sometimes reaching a degree of impairment comparable to progressive Alzheimer's disease — was not related to the same neurological defects as Alzheimer's. Where Alzheimer's disease is associated with plaque deposition and tangled ganglia formations, Parkinson's dementia is thought to be produced by neurotransmission abnormalities. Research found:

…in Parkinsonian patients with dementia there were extensive reductions of choline acetyltransferase and less extensive reductions of acetylcholinesterase in all four cortical lobes. Choline acetyltransferase reductions in temporal neocortex correlated with the degree of mental impairment assessed by a test of memory and information but not with the extent of plaque or tangle formation. In Parkinson's but not Alzheimer's disease the decrease in neocortical (particularly temporal) choline acetyltransferase correlated with the number of neurons in the nucleus of Meynert, suggesting that primary degeneration of these cholinergic neurons may be related, directly or indirectly, to declining cognitive function in Parkinson's disease. (Perry et al., 1985, p. 413)

Cognitive function is therefore impaired by chemical rather than structural means: when the production of necessary neurotransmitters is disrupted, or when cells are unable to uptake these chemicals, dementia may result, most often in the late stages of the disease. Additionally, the later the disease develops symptoms, the more commonly dementia and other cognitive impairments are observed, and these impairments can often be present even in cases where motor impairments are absent or minimal (Perry et al., 1985, pp. 413–421).

Sadly, because a great deal of knowledge on this subject is specialized and scholarly, patients who exhibit atypical Parkinsonian cognitive impairment — such as dementia unaccompanied by motor impairments — are often not screened for Parkinson's and may be overlooked for appropriate treatment. Because the disease develops differently in different individuals, it can be easily misdiagnosed, particularly in dementia cases, and treated as Alzheimer's disease. Although Alzheimer's has limited treatments, its treatment regimen will not positively affect Parkinsonian dementia or other PD symptoms. This kind of masked, atypical Parkinson's presentation should demand more rigorous identification of the etiology underlying Alzheimer's and other dementia diagnoses. Risk factors associated with environmental exposure and emerging research in genetic predisposition will likely help address this oversight (NINDS, 2010).

Conclusion: Toward an Integrated Understanding

Current trends in research demonstrate that cognitive and emotional functioning impairments may be discrete from one another but occur simultaneously and can be seen as nearly universal in PD patients compared to healthy individuals. As one study noted, "The performance of the patients in memory tests and other tests evaluating cognitive capacity did not correlate either with their motor disability or with their mood. A possibility therefore exists that biological processes behind the cognitive decline and the motor disability are separate, even if they may occur simultaneously" (Hietanen & Teräväinen, 2009, pp. 151–159).