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Cognitive Symptoms Of Parkinson’s Disease

Parkinson’s Disease Dementia Versus Dementia With Lewy Bodies

Cognitive and Non-motor Symptoms of Parkinson’s Disease

Parkinson’s disease dementia is a form of Lewy body dementia. Lewy bodies form in the brain and clump together in nerve cells. These nerve cells with Lewy bodies lose their function.

There is another condition known as dementia with Lewy bodies . In both PDD and DLB, Lewy bodies form in the brain and cause nerves to malfunction.2,3

Parkinson’s and dementia with Lewy bodies have very similar symptoms including cognitive dysfunction and parkinsonian movement symptoms.

The main difference between the 2 conditions is timing. Motor symptoms are common in people with early PD, and dementia may develop much later. In people with DLB, motor symptoms and dementia begin together or the dementia appears soon after movement symptoms. It can be hard for your doctor to tell if you have Parkinson’s or DLB at the early stages of either condition.3,4

What Cognitive Changes Should You Expect

Between 20% and 50% of people with Parkinsons have mild cognitive changes at some point, even early on. You may not even notice them if they dont get in the way of with your daily life.

Mild cognitive changes with Parkinsons may crop up as problems with:

  • Memory or recall

Cognitive screening tests. The doctor can give you questionnaires to measure your cognitive function, like:

  • Mini-Mental State Examination
  • Montreal Cognitive Assessment

These screening tests only take 10 minutes or less to complete. The doctor will ask you questions and assess your memory, speech habits, awareness, concentration, problem-solving skills, and movements.

Referrals to specialists. A clinical neuropsychologist can give you more formal tests to figure out if you have mild cognitive changes due to Parkinsons, or if your symptoms result from another condition like a stroke or Alzheimers disease.

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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Why Does Parkinsons Cause Cognitive Changes

The cause of cognitive changes in PD is not fully understood. But the damage to multiple areas of the brain caused by PD is probably responsible. The basal ganglia and frontal lobes are 2 areas of the brain that are commonly affected in PD. These areas play a role in thinking skills and executive functions, which are the skills needed to carry out a task. It is also possible that the drugs used to treat PD may add to cognitive changes.1

Preventing And Delaying Cognitive Change

Symptoms

To overcome the cognitive changes linked to Parkinsons, it is recommended that you keep as active and stimulated as possible – physically, mentally and socially. It is important to stimulate all the different parts of the brain. Some useful tips include:

  • Undertake regular exercise
  • Complete simple arithmetic and crosswords
  • Listen to and play music
  • Participate in a social group
  • Do volunteer work
  • Maintain paid employment if possible
  • Learn new skills

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When To See A Healthcare Provider

In general, if you suspect you have Parkinsons disease and are experiencing typical symptoms, such as tremors, rigidity, and difficulty with motion or staying upright, you should call your healthcare provider. Seek out emergency care if you are experiencing any of the following symptoms :

  • Sudden onset of or changes to the pattern of your symptoms
  • Severe reactions or lack of response to medications
  • Any cognitive symptoms, such as difficulty remembering or concentrating

Study Design: Systematic Review

Literature search for published studies

We conducted a systematic search for all controlled trials regarding pharmacologic and non-pharmacological interventions for falls in PD that were published as full text papers up to May 2015. We used the electronic databases Medline, EMBASE, Cochrane Library Central Database and PEDro using the MeSH terms PD, or Parkinson disease AND falls AND intervention AND prevention to complete the literature search. Full text copies of potentially relevant trials were retrieved and their reference lists were systematically checked.

Literature search for ongoing studies

We also analyzed the major characteristics of ongoing clinical trials from the online open-access World Health Organization , the Clinical trial.gov database and the European Clinical Trials database that proposed to evaluate the efficacy and/or safety of therapeutic interventions for the prevention or management of falls in PD. Within these databases, a search was performed for ongoing controlled trials regarding PD and falls using the following keywords: Parkinson disease AND falls. The studies were hand sorted to exclude duplicate entries and studies that were not related to therapeutic interventions for falls in PD. Data regarding study variables, particularly exclusion on the grounds of cognitive scores were extracted from each study.

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Csf Biomarkers In Pdd

Many studies on CSF aimed to identify biomarkers reflecting the abnormal protein aggregates associated with PDD. In the majority of them, the level of Aß was found reduced4952 whereas the levels of total and phosphorylated tau were increased49,50,53,54 or unchanged52,55 in PDD. The use of more or less strict definition for dementia and the inclusion of more or fewer patients with AD- memory problems can partially account for the discrepancies in the tau level reported.

Based on the data from cross-sectional and longitudinal studies there is the strongest evidence that low levels of A and increased levels of tau in the CSF at baseline might predict future cognitive decline in patients with PD.5659

We performed a longitudinal study in non-demented PD patients including CSF, neuropsychological and MRI at baseline and 18 months follow-up.60 We found that a combination of lower CSF A, reduced verbal learning, semantic uency, and visuoperceptual scores, as well as cortical thinning in superior-frontal/anterior cingulate and precentral regions, were predictive for PDD. In this sense, different studies have shown that a combination of clinical, biological, and neuroimaging markers could be predictive for deterioration in cognition in PD with good accuracy.59,61,62

Prescription Medications To Treat Parkinsons

Everything Parkinson’s: Cognitive Symptoms in Parkinson’s Disease

Most movement symptoms are due to a lack of dopamine. Therefore, drugs prescribed to treat PD are dopaminergic they either replenish dopamine or mimic its effects on the brain. The most common is called levodopa. The body converts this medication into dopamine to help control movement symptoms.

Make sure your doctor knows all medications you take including over-the-counter and supplements. This helps reduce the risk of drug interactions, a common issue for Parkinsons patients.

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Genetics Of Pd Dementia

Although the genetic risk factors for PD have been investigated, much less is known about the genetic factors associated with the development of dementia in PD. According to some studies, the prevalence of PDD is lower in patients with genetic PD. However, this will depend on the gene variant and other comorbidities that predispose the development of cognitive disorders. Some of the most important genes are discussed below:

PARK1: patients with duplication or triplication of alpha-synuclein gene have more severe motor progression and worse cognitive prognosis compared to those without the mutation. Although the evidence suggests that the higher the number of replications, the lower the age of onset of cognitive impairment. Of all genes, this seems to be the most related to dementia. More studies are needed to confirm these findings .

  • PARK2: according to some case series, mutations in PARK2 do not seem to cause cognitive decline .

  • PARK14: PLA2G6 mutation could show heterogeneous phenotype including dementia.

  • DJ-1: due to its low prevalence, there is no clear relationship between DJ-1 and a particular PD cognitive phenotype. There are some reports of dementia within the clinical spectrum of DJ-1 mutations. In a large population-based survey, there was no evidence for an increased risk of dementia in carriers of DJ-1 deletion .

  • PINK1: due to its low prevalence, there is conflictive evidence on the relation between PINK1 and PD dementia or cognitive decline .

  • Dementia And Parkinson’s Disease

    In this 2-hour webinar geriatrician Naaz Parmar provides an understanding of dementia as a disease, the different subtypes of dementia, and how they affect a person with concurrent PD. This webinar also gives an overview of treatment options with lifestyle changes and medications. Coping strategies for a person with dementia and their loved ones, will also be discussed.

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    Experimental Models Of Cognitive Impairment For Use In Parkinsons Disease Research: The Distance Between Reality And Ideal

    • 1Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Shenzhen, China
    • 2Guangzhou University of Chinese Medicine, Guangzhou, China
    • 3Shenzhen Baoan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, China

    How Is Parkinson Disease Diagnosed

    Typical Age For Parkinson

    Parkinson disease can be hard to diagnose. No single test can identify it. Parkinson can be easily mistaken for another health condition. A healthcare provider will usually take a medical history, including a family history to find out if anyone else in your family has Parkinson’s disease. He or she will also do a neurological exam. Sometimes, an MRI or CT scan, or some other imaging scan of the brain can identify other problems or rule out other diseases.

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    Systematic Literature Search On Experimental Models Of Parkinsons Disease Cognitive Impairment

    To clarify trends in experimental modeling of PD cognitive impairment, we systematically searched PubMed using the following search terms: OR OR OR . The publication range was from the start of the database to 30 May 2021. Two investigators reviewed each topic and abstract independently to select references that met the inclusion criteria. Inconsistencies encountered by the reviewers would be resolved after consultation with a third reviewer . The selection process is shown in Figure 1. We identified 5432 articles, of which 738 were duplicates. A total of 227 articles met our inclusion criteria and were included in the analysis.

    Figure 1. Flow chart for the selection of studies.

    Figure 2. Trends in experimental models of PD with cognitive impairment.

    Pharmacologic Management Of Pdd

    There are increasing literature studies about PDD treatment at home and abroad. It is believed that one of the main solutions is to control its motor symptoms, and the other is to delay the development of cognitive impairment.

    The mainstay of therapies for PDD is drug administration, including cholinesterase inhibitor and memantine. Patients with PDD have more decreased cholinergic levels of the cerebral cortex than AD individuals, which may serve as the biological basis of the effectiveness of anticholinesterase drugs .

    Rivastigmine, the second generation of central acetylcholinesterase inhibitor, selectively inhibits cholinesterase in the cerebral cortex and hippocampus. A large randomized controlled trial showed that rivastigmine can significantly improve overall cognitive function and clinical manifestations of PDD compared with placebo, which is the only medication confirmed to be effective for PDD . Atomoxetine can selectively inhibit the reuptake of norepinephrine, a neurotransmitter related to cognitive function. There was also a systematic review which described atomoxetine had positive effects on executive function in multiple RCTs . Whether these therapies can slow the progression of transition from PD-MCI to PDD is a key question for future research.

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    What Happens In Pdd

    People with PDD may have trouble focusing, remembering things or making sound judgments. They may develop depression, anxiety or irritability. They may also hallucinate and see people, objects or animals that are not there. Sleep disturbances are common in PDD and can include difficulties with sleep/wake cycle or REM behavior disorder, which involves acting out dreams.

    PDD is a disease that changes with time. A person with PDD can live many years with the disease. Research suggests that a person with PDD may live an average of 57 years with the disease, although this can vary from person to person.

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    Symptoms Of Cognitive Change

    The Parkinson’s You Don’t See: Cognitive and Non-motor Symptoms

    The cognitive changes experienced by people with Parkinsons vary from person to person. Possible cognitive symptoms linked with early-stage Parkinsons include:

    • Difficulty multi-tasking
    • Difficulty concentrating and becoming easily distracted
    • Difficulty learning new skills
    • Difficulty remembering certain things

    As Parkinsons progresses these symptoms can worsen and new symptoms might appear. Possible impairments later in the course of the condition might include:

    • Difficulty with problem-solving
    • Difficulty judging distances and directions

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    Biomarkers Of Cognitive Decline

    Many of the pathologies associated with cognitive impairment can be identified in vivo using a variety of imaging and blood-based or CSF-based markers. These biomarkers can be used to provide an increased understanding of the mechanisms underlying cognitive impairment in PD and, from a clinical perspective, can identify patients with an increased risk of early and rapid cognitive decline.

    One of the first identified predictive markers was temporo-parietal atrophy on MRI , confirmed in many subsequent studies. In addition, basal forebrain atrophy observed using MRI is also associated with cognitive impairment in PD,. Hypometabolism in the medial frontal and parietal regions using FDG-PET is associated with a decline in executive and memory function. More recent MRI techniques, such as diffusion tensor imaging, also hold promise as biomarkers of cognitive function. For example, increased radial and axial diffusivity in the thalamus observed using diffusion tensor imaging was associated with a decline in MoCA scores.

    Patient And Public Involvement

    In the past years, there has been growing attention on the need to include patients, their caregivers and families in all stages of the research process. The increasing contribution of patient and public involvement groups in defining research questions, designing and conducting clinical trials, disseminating outcomes, and shaping research roadmaps reflects the concept of research as a shared effort among all stakeholders. Although in PD research this concept is increasingly being recognized, further involvement of patients and families, also inclusive of diverse patient populations, in research focused on PD-associated cognitive impairment is needed.

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    Cognitive Impairment In Parkinsons Disease

    Cognitive impairment is a common non-motor symptom of Parkinsons disease and causes significant disability to patients and burdens for caregivers. Similar to motor symptoms, the characteristics of cognitive impairment in Parkinsons disease can be quite variable, both in terms of what cognitive domains are impaired and the timing of onset and rate of progression.

    Predictors Of Psychiatric Symptoms

    Parkinsons Disease Infographic in 2021

    The PD patients remained more likely to meet the GDS cutoff score for depression compared with HCs when controlling for demographic characteristics . Examining raw GDS scores in PD patients only, being non-white, higher MDS-UPDRS motor scores, and non-TD motor subtype were associated with increasing severity of depression . Using the GDS cutoff score in PD patients only, being non-white and having non-TD motor subtype was associated with depression, with a trend effect for higher MDS-UPDRS motor score .

    In a multivariate model, having PD was not associated with presence of ICD symptoms when controlling for demographic factors . Examining only PD patients, no demographic or clinical factors predicted a positive QUIP .

    Younger age, higher MDS-UPDRS motor scores, shorter duration of disease, and non-TD motor subtype were associated with more severe state anxiety in a multivariate model . Trait anxiety was associated with younger age, higher MDS-UPDRS motor scores, non-TD motor subtype, being non-white, and female sex .

    No demographic or clinical predictors of a positive psychosis score were seen on the MDS-UPDRS item in PD patients. Increasing disability and non-TD motor subtype = 2.14 , df = 1, P = 0.005) predicted a positive apathy score. The PD patients with apathy had higher depression scores than patients without apathy , but there was no association with global cognition .

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    Other Reasons For Cognitive Symptoms

    Besides PD, there are other important causes of cognitive dysfunction to keep in mind. Medical illnesses such as thyroid disease or vitamin B12 deficiency can cause cognitive symptoms. Urinary tract infections or pneumonia can acutely cause confusion or hallucinations. In these settings, the cognitive symptoms are generally reversible after the infection or medical condition is treated. One should be aware that some medications for pain or bladder problems may cause sedation/sleepiness or confusion, and, thereby, impair cognitive function.

    Classification Issues And Prodromal Stages

    The proposal that dementia prior to or simultaneous with motor symptoms can be included in the diagnostic criteria for PD, has reopened the long-standing debate on whether PDD and DLB should be considered the same disease,,,. A deeper understanding of the pathophysiological processes underlying these two synucleinopathies, such as the relative contribution of -amyloid and tau pathology in cortex and striatum, the extent of cortical Lewy pathology and -synuclein load in the hippocampus, the severity of neuronal loss in the substantia nigra, and cholinergic cell loss, is required to better understand the relationship between PD and DLB.

    Although some risk factors for cognitive impairment have been identified,,, further research is needed to better identify any early evidence of cognitive impairment in genetic at-risk populations and in individuals with clinical features of prodromal PD to provide opportunities for prevention strategies and early precision therapy interventions.

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