Causes Of Cognitive Impairment In Pd
The exact causes of cognitive impairment or dementia in Parkinsons disease are not fully understood. There may be changes in the neurochemical signals that the brain uses to pass along information to different regions of the brain. Besides dopamine, the neurochemical signals acetylcholine, serotonin, and norepinephrine are especially important for cognition, memory, attention, and mood. In autopsy studies, Lewy bodies, abnormal protein accumulations, have been found in neurons in brain regions responsible for cognitive processes. Other causes include co-existing strokes or mini-strokes or Alzheimers disease pathology.
What Is Parkinson Disease
Parkinson disease is a movement disorder. It can cause the muscles to tighten and become rigid This makes it hard to walk and do other daily activities. People with Parkinsons disease also have tremors and may develop cognitive problems, including memory loss and dementia.
Parkinson disease is most common in people who are older than 50. The average age at which it occurs is 60. But some younger people may also get Parkinson disease. When it affects someone younger than age 50, it’s called early-onset Parkinson disease. You may be more likely to get early-onset Parkinson disease if someone in your family has it. The older you are, the greater your risk of developing Parkinson disease. It’s also much more common in men than in women.
Parkinson disease is a chronic and progressive disease. It doesn’t go away and continues to get worse over time.
Navigating Cognitive Changes In Parkinsons Disease: A Guide For Patients And Families
Cognitive change is a common non-motor symptom of Parkinsons. Attention, memory, executive function, language and visuospatial skills may be affected. This 35-page booklet shares ways boost brain health and how to keep track of cognitive changes. It defines mild cognitive impairment and dementia, and shares treatments and management tips for dementia, hallucinations and delusions. It encourages families to communicate about cognitive change and cites areas of ongoing research in dementia.
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Parkinsons And Lewy Body Disease
Lewy body disease occurs when there is an abnormal build-up of a protein called alphasynuclein in the brain. Depending on where the proteins accumulate, Lewy body disease can lead to impairments in movement, thinking and behaviour.
Lewy body disease includes three overlapping disorders:
- Dementia with Lewy bodies
- Parkinsons disease dementia
This overlap results in the disease being called a spectrum disease.
In people with Parkinsons a large number of Lewy bodies appear in an area of the brain known as the substantia nigra. This area of the brain is responsible for movement, so the Lewy bodies are likely to cause impairments in movement.
Some people may go on to develop dementia with Lewy bodies. In this form of the disease, the clumps of protein occur in the cortex . This part of the brain is responsible for many cognitive processes, so the Lewy bodies are likely to result in cognitive impairments like those described under the heading above. It can result in symptoms similar to those seen in Alzheimers.
Mimicking Human Conditions In Animal Models
With the advance of the medical research, it is possible to mimic certain human conditions in selected animals, such as mouse or rat, to study the development of a disease and search for treatment. In addition to being very close to the human physiology, these animal models are reliable and critical to develop new treatment strategy and to understand the pathophysiology of a disease.
In the laboratory of Professor Musa V. Mabandla, we have by exposing pups to early maternal separation once daily, from post-natal day 1 to 14. We thereafter injected these rat models with depressive-like behaviors with a preclinical dose of 6-hydroxydopamine stereotaxically into the medial forebrain bundle to mimic Parkinsonism. This has resulted to a rat model of PD associated with depressive-like behaviors.
We also injected these animal models with Fluvoxamine maleate , an antidepressant widely used for the treatment of psychiatric disorders, to investigate the neuroprotective effects of the drug on a parkinsonian rat model of neurodegeneration.
Our findings show that early maternal separation exacerbated the effects of 6-hydroxydopamine, but FM treatment attenuated neurodegeneration associated with 6-hydroxydopamine toxicity.
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Comparison With Other Dementias
Dementia is the result of physical changes in the brain that can lead to memory loss and an inability to think clearly.
Several types of dementia exist, including:
PD dementia has different symptoms to other types.
Alzheimers dementia, for example, impairs memory and language. PD dementiam on the other hand, affects problem-solving, the speed at which thoughts occur, memory, and mood, alongside other important cognitive functions.
Dementia with Lewy bodies and Parkinsons disease dementia are similar in that the Lewy Bodies might be present in both forms.
However, whether the disease causes Lewy bodies or if Lewy bodies cause the disease symptoms is unclear. Researchers also believe that the way the Lewy bodies form in Parkinsons disease dementia is different from those in Lewy body dementia.
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How Is Psp Diagnosed
Currently there are no tests or brain imaging techniques to definitively diagnose PSP. An initial diagnosis is based on the persons medical history and a physical and neurological exam. Identifying early gait problems, problems moving the eyes, speech and swallowing abnormalities, as well as ruling out other similar disorders is important. Diagnostic imaging may show shrinkage at the top of the brain stem and look at brain activity in known areas of degeneration.
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Medicines For Parkinsons Disease
Medicines can help treat the symptoms of Parkinsons by:
- Increasing the level of dopamine in the brain
- Having an effect on other brain chemicals, such as neurotransmitters, which transfer information between brain cells
- Helping control non-movement symptoms
The main therapy for Parkinsons is levodopa. Nerve cells use levodopa to make dopamine to replenish the brains dwindling supply. Usually, people take levodopa along with another medication called carbidopa. Carbidopa prevents or reduces some of the side effects of levodopa therapy such as nausea, vomiting, low blood pressure, and restlessness and reduces the amount of levodopa needed to improve symptoms.
People living with Parkinsons disease should never stop taking levodopa without telling their doctor. Suddenly stopping the drug may have serious side effects, like being unable to move or having difficulty breathing.
The doctor may prescribe other medicines to treat Parkinsons symptoms, including:
- Dopamine agonists to stimulate the production of dopamine in the brain
- Enzyme inhibitors to increase the amount of dopamine by slowing down the enzymes that break down dopamine in the brain
- Amantadine to help reduce involuntary movements
- Anticholinergic drugs to reduce tremors and muscle rigidity
Impact Of Pd Treatments
The clinical choice of initial PD medication inhibitor) at disease onset does not seem to make a difference in terms of cumulative dementia rates,. However, there is strong evidence that medications with anticholinergic properties , and particularly the long-term exposure to multiple medications or medications with greater anticholinergic properties, are associated with worse long-term cognition in the general population and patients with PD,, and thus represent a target for clinical management. In patients with PDD, simplification of antiparkinsonian treatment through a stepwise withdrawal of non-levodopa PD medications starting with anticholinergic drugs, followed by amantadine, selegiline, dopamine agonists and then catechol-O-methyltransferase inhibitors, might be useful, particularly if comorbid psychosis is present.
In addition, several studies have found that DBS can worsen cognitive functioning as a result, cognitive testing is recommended as part of the pre-DBS surgery evaluation process, and patients with severe cognitive impairment should not undergo brain surgery. However, the use of model-based stimulation parameters to minimize the spread of the electrical current to non-motor portions of the subthalamic nucleus reversed the cognitive decline that occurred after DBS in one study. Encouragingly, a subsequent study of DBS in younger patients with shorter disease duration showed short-term cognitive tolerability similar to the best medical therapy.
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Parkinsons Disease: Causes Symptoms And Treatments
Parkinsons disease is a brain disorder that causes unintended or uncontrollable movements, such as shaking, stiffness, and difficulty with balance and coordination.
Symptoms usually begin gradually and worsen over time. As the disease progresses, people may have difficulty walking and talking. They may also have mental and behavioral changes, sleep problems, depression, memory difficulties, and fatigue.
While virtually anyone could be at risk for developing Parkinsons, some research studies suggest this disease affects more men than women. Its unclear why, but studies are underway to understand factors that may increase a persons risk. One clear risk is age: Although most people with Parkinsons first develop the disease after age 60, about 5% to 10% experience onset before the age of 50. Early-onset forms of Parkinsons are often, but not always, inherited, and some forms have been linked to specific gene mutations.
Improved Clinical Trial Design
Clinical trials for therapies targeting cognition in PD may benefit from recent design improvements. More sensitive outcomes, including computerized cognitive testing and wearables to measure motor and other functions, together with the development of an internationally recognized set of core outcomes, as has been done for idiopathic PD, particularly focused on patients with cognitive impairment and on the effects of specific interventions , will allow the reporting and comparison of research outcomes in a standardized manner. More targeted selection criteria using current diagnostic criteria, and recommended assessments, combined with both biomarkers and genetic risk factors aiming to assign the right person to the right intervention at an early disease stage, as well as biomarkers demonstrating target involvement, will offer opportunities for improved statistical power and cheaper trials.
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Prognosis Of Parkinsons Disease
As Parkinsons progresses, symptoms often worsen. Some people who respond well to therapy have minimal disability issues. Others, however, become severely incapacitated.
Although Parkinsons isnt considered a fatal disease itself, it can cause life-threatening complications that may shorten your life span.
Today, most people living with Parkinsons disease have close to a normal life expectancy.
Number Of People Affected
Parkinson’s disease is thought to affect about 2 percent of Americans over 65. Of those, about 50 to 80 percent will go on to develop Parkinson’s-related dementia.1 The Parkinson’s Foundation estimates that nearly 1 million Americans will be living with Parkinson’s by 2020. The disease affects 1.5 times more men than women.7
Approximately 5.8 million Americans are currently living with Alzheimer’s disease. That number is expected to increase to 14 million by 2050.8 There is little difference between the numbers of men and women who develop Alzheimer’s, but there are more women with the disease because women tend to live longer than men.3
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At What Stage Of Parkinsons Does Dementia Start
If people with Parkinsons develop dementia, it is usually in the later stages of the disease.
Dementia may not affect everyone who has Parkinsons. An estimated 40% of those with Parkinsons also have dementia.
A longer duration of Parkinsons, significant movement difficulties, MCI, hallucinations, and delusions may increase the risk of developing dementia with Parkinsons.
Mild Memory And Thinking Problems
Mild memory and thinking problems can be a normal part of getting older. But sometimes, these symptoms are caused by Parkinsons.
Mild memory and thinking problems are symptoms such as forgetfulness, problems concentrating and difficulty making decisions, but you can still manage your day-to-day life.
They are common in Parkinsons and can happen at any stage of the condition, but not everyone with Parkinson’s has these symptoms.
If you do experience these symptoms, your doctor may describe it as a mild cognitive impairment .
Its normal to worry if youre experiencing memory and thinking problems, but it doesnt necessarily mean you have dementia, or that you will develop it in the future.
You might have problems with activities such as planning, multitasking and moving quickly from one activity to another, or doing tasks in a particular order.
This may mean you feel less efficient or less organised than you used to be, or you may get confused, particularly if youre feeling stressed.
Problems with attention and concentration can also make everyday activities more difficult, such as reading a newspaper article from start to finish.
You might experience slowed thinking, so it could take you longer to make decisions or respond to questions.
If youve had surgery for Parkinsons, such as deep brain stimulation , you may have some specific symptoms, such as problems with talking, concentration and complex thinking. But some people find that the surgery improves their memory.
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Symptoms Of Parkinsons Disease
Parkinsons has four main symptoms:
- Tremor in hands, arms, legs, jaw, or head
- Muscle stiffness, where muscle remains contracted for a long time
- Slowness of movement
- Impaired balance and coordination, sometimes leading to falls
Other symptoms may include:
The symptoms of Parkinsons and the rate of progression differ among individuals. Early symptoms of this disease are subtle and occur gradually. For example, people may feel mild tremors or have difficulty getting out of a chair. They may notice that they speak too softly, or that their handwriting is slow and looks cramped or small. Friends or family members may be the first to notice changes in someone with early Parkinsons. They may see that the persons face lacks expression and animation, or that the person does not move an arm or leg normally.
People with Parkinson’s disease often develop a parkinsonian gait that includes a tendency to lean forward take small, quick steps and reduce swinging their arms. They also may have trouble initiating or continuing movement.
Symptoms often begin on one side of the body or even in one limb on one side of the body. As the disease progresses, it eventually affects both sides. However, the symptoms may still be more severe on one side than on the other.
Degeneration Of Neurotransmitter Systems
More widespread dopaminergic deficits in the brain
By definition, all patients with PD have a moderate-to-severe loss of dopaminergic neurons in the nigrostriatal projection pathway. More widespread degeneration of dopaminergic terminals in the striatum particularly denervation of dopaminergic terminals in the associative dorsal caudate nucleus occurs in those with PD-MCI than in those with PD without cognitive impairment . However, in patients with PD-MCI, there is relative preservation of other dopaminergic systems in the brain, whilst those with PDD have a considerable loss of the lateral dopaminergic system to frontal, parietal and temporal cortical regions . In healthy individuals, cortical dopamine modulation can boost working memory as well as visuospatial and attentional processing, and promotes cognitive effort,, suggesting a key role for dopamine in cognitive function.
Fig. 2: Neurotransmitter deficits associated with cognitive decline in PD and DLB.
Other pathology
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What Are The Risk Factors For Parkinsons Disease
Risk factors for Parkinsons disease include:
Genetics
People with a first-degree relative with Parkinsons are at an increased risk for the disease possibly as much as 9 percent greater.
Fifteen percent of people with Parkinsons have a known relative with the disease, but a condition called familial Parkinsons, which has a known genetic link, is relatively rare.
The average age of onset is 60 years, and the incidence rises with advancing age. About 4 percent of people have early-onset or young-onset disease, which begins before age 50.
Gender
Parkinsons affects about 50 percent more men than women, for unknown reasons.
Pesticide Exposure
Exposure to some pesticides has been shown to raise the risk of developing Parkinsons.
Problematic chemicals include organochlorine pesticides like DDT, dieldrin, and chlordane. Rotenone and permethrin have also been implicated.
Fungicide and Herbicide Exposure
Exposure to the fungicide maneb or the herbicides 2,4-dichlorophenoxyacetic acid , paraquat, or Agent Orange may raise the risk of Parkinsons.
The U.S. Veterans Health Administration considers Parkinsons to be a possible service-related illness if the person was exposed to significant amounts of Agent Orange.
Head Injuries
Head injuries may contribute to the development of Parkinsons in some people.
Coffee and Smoking
People who drink coffee or smoke tobacco have been found to have a lower risk of Parkinsons disease, for reasons that remain unclear.
Clinical Value Of The Present Findings
Our PD participants had problems in WM updating that were unrelated to their other cognitive difficulties, such as prolonged response latencies, difficulties in maintaining attention and inhibiting irrelevant information, and episodic memory deficits. As compared to other WM subdomains, updating was the only subdomain that clearly discriminated PD patients from healthy controls even when no other problems were considered. Altogether, these findings suggest that the WM subdomain of updating should receive particular attention when surveying onset cognitive deficits in PD patients. However, further test development is needed to utilize this knowledge in practice, as standardized, readily available measures of WM updating are lacking.
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Prodromal Pd Phenotypes And Conversion
Recent evidence suggests that individuals with prodromal features of PD, such as hyposmia , REM sleep behaviour disorder and reduced dopamine transporter binding, may present with worse cognitive performance compared with people without any or with only one of these features,,. Interestingly, prodromal PD and DLB may overlap and it is not yet known how to distinguish between those who will develop PD versus those who will develop DLB. Of note, cognitive deficit has been recently defined as a new prodromal marker and has been included in the last update of the research criteria for prodromal PD.
How Is Parkinsons Disease Diagnosed
There arent any specific tests to diagnose someone with Parkinsons disease.
Doctors typically make a diagnosis based on the following:
- Medical history
- Blood and lab tests
Sometimes, people who have a known inherited form of Parkinsons disease can take a gene test to determine their risk for developing the disease.
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