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Monday, June 10, 2024
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Parkinson’s Disease Cognitive Impairment

Clinical Features And Diagnostic Criteria

Ask the MD: Cognitive Impairment and Parkinson’s Disease

The clinical picture of VP is heterogeneous. Several clinical features have beendescribed relating brain vascular lesions to Parkinsonism. A clinical diagnosis ofVP remains difficult to establish as infarction of the basal ganglia and deep whitematter occur frequently in elderly people who do not have Parkinsonism and vascular lesions are a commonincidental finding in pathologically-confirmed PD. Hence, a large proportion of patients withlate-onset PD have some degree of white-matter change on CT/MRI brain scans.

Given its clinical heterogeneity, Fénelon and Houéto stratified VP into four typesaccording to clinical manifestations:

  • VP manifesting in a manner identical to PD

  • unilateral Parkinsonism following contralateral vascular lesion

  • atypical Parkinsonian syndromes

  • Parkinsonian gait disorders.

Unilateral Parkinsonian syndromes caused by contralateral vascular lesions representpure VP, whose criteria include the appearance of unilateral Parkinsonismfollowing an ischemic and haemorrhagic stroke in the substantia nigra, thalamus orat strategic locations that disrupt the striatopallidal loop. Striatal or striatopallidalischemic lesions have been more frequently observed than substantia nigralesions.,,

In 2004, Ziljmans et al. proposednew clinical criteria for diagnosing VP based on their clinico-pathological findings.

Description Of Cognitive Impairment

Cognitive impairment in Parkinsons disease is characterized by predominant executive function deficits, attention difficulties, visuospatial dysfunction, slowed thinking, difficulties in word-finding, and difficulties in learning and remembering information.

Many people with Parkinsons disease feel distracted or disorganized, or have difficulty planning and carrying out tasks. It may be harder for patients to focus in situations that divide their attention, like a group conversation. When facing a task or situation on their own, Parkinsons disease patients may feel overwhelmed by having to make choices. They also may have difficulty remembering information, or have trouble finding the right words when speaking. For some, these changes are merely annoying for others they interfere with work or with managing household affairs.

Cognitive changes in patients can range from Parkinsons disease mild cognitive impairment to Parkinsons disease dementia . PD-MCI can be detected only by various means of comprehensive neuropsychological observations and normally does not affect the patients daily operations. PDD hits more than one area of cognition and is severe enough to impair social or working functions.

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.

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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

Thinking Changes In Parkinson’s


In this 1-hour webinar Travis Turner, PhD, explains why you might be referred for a neuropsychological evaluation, what is done during such an evaluation, how the information learned during an evaluation is used, and tips for performing your best during an evaluation. After the talk he answered several questions about coping with cognitive changes when you have PD or are caring for someone with PD.

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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:

Is There A Proposed Mechanism Of Vascular Parkinsonism

Ischemic basal ganglia or subcortical white matter lesions disrupt interconnecting fiber tracts between the basal ganglia, thalamus, and motor cortex leading to disruption of sensory-motor integration as well as descending reticular pathways to major centers of the brain stem.

Infarctions affecting basal ganglia lacunae, including the thalamus, external globus pallidus, and putamen, that extend into the caudate and internal capsule, can mimic features of idiopathic PD. The second form with subcortical white matter lesions often produces clinical features resembling the classical lower body parkinsonism and has a more relentless rather than step-wise progression.

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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.

Ask The Md: Cognitive Impairment And Parkinsons Disease

Thinking and Memory Problems with Parkinson Disease

This 4:27-minute video is an explanation of cognitive changes that can happen in Parkinsons disease. Dr. Rachel Dolhun explains how doctors evaluate cognitive changes to exclude other conditions that may be correctable. She distinguishes between mild cognitive impairment and dementia, with some treatments for each.

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Atomoxetine For Cognitive Impairment In Parkinsons Disease

Objective/Rationale:Parkinsons disease causes well known motor symptoms of tremor, slowness and stiffness, but also leads to cognitive impairment. Research has shown that early loss of cells in a brain structure called the norepinephrine-locus ceruleus in PD corresponds with the development of cognitive deficits and is a novel target for PD therapeutics. Atomoxetine is a specific norepinephrine reuptake inhibitor, which increases the availability of this critical neurotransmitter at the brain level. Researchers hypothesize that treatment with ATM will improve attention, set-shifting, information processing speed and working memory in cognitively impaired people with PD.

Project Description: This is an early Phase II trial to prove the concept that ATM can improve certain aspects of cognitive function in PD. Investigators will accomplish this with a double-blind, placebo-controlled trial of ATM in 30 cognitively impaired, non-demented people with PD. They hypothesize that ATM will improve attention, set-shifting, information processing speed and working memory without compromising motor function. Thirty study subjects will be randomized to receive either ATM or placebo. A carefully designed neuropsychological test will be administered at baseline and after 10 weeks of ATM treatment.

Anticipated Outcome:The proposed work is expected to demonstrate whether ATM is worth pursuing with a larger, definitive clinical trial.

Cognitive Issues: Advice For Parkinsons Care Partners

In this 1-hour webinar, movement disorder specialist Dr. Rebecca Gilbert discusses why cognitive issues are part of PD, types of cognitive issues in PD, modifiable causes of cognitive issues, what can improve cognition, the impact psychosis and visual hallucinations on people with PD, lifestyle modifications that can improve quality of life for both the person with PD and their care partner.

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Correlates And Predictors Analysis

Linear regression analysis showed significant associations between higher PD-CRS total score and younger age , education level and lower UPDRS-III . Significant associations independent of age, education and motor status were also found between the PD-CRS total score and the NPI apathy score .

In the bivariate Pearsons correlation analysis performed in the total sample, the PD-CRS total score was negatively associated in an almost negligible range with the levels of Il2 , Il6 , homocysteine and iron . However, these values were also strongly associated with age and LD daily dose. Accordingly, to prevent the potential influence of age and LD, these variables were included as covariates in a linear regression model. This analysis showed a significant association between PD-CRS total score and vitamin B12 values , homocysteine levels and iron levels , and a specific mild association between PD-CRS posterior-cortical performance and IL2 values .

Preventing And Delaying Cognitive Change

metabolic profiling of Parkinson

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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Psychiatric & Cognitive Complications In Parkinsons

Depression, anxiety, cognitive decline, psychosis and impulse control can be common in people with Parkinsons. They affect quality of life for both people with Parkinsons and care partners. In this webinar Dr Daniel Weintraub discusses these issues, the correlation between mood, motor function and Levodopa levels, and more. Registration is required, but it is free.

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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Neurochemical Deficits In Pdd

Degeneration of subcortical nuclei in PD leads to dopaminergic, cholinergic, noradrenergic, and serotoninergic deficits. Of them, cholinergic deficits due to degeneration of the nucleus basalis of Meynert have been the most involved in PDD. In early neuropathological studies, PDD patients showed more NMB cholinergic neuronal depletion when compared with AD and non-demented PD.33,34 A greater reduction of choline acetyltransferase activity in frontal and temporal cortex was found in PDD than in PD without dementia.35 Mattila et al reported reduced choline acetyltransferase activity in the hippocampus, prefrontal cortex, and temporal cortex in PD. Reduction in the frontal cortex correlated signicantly with the degree of cognitive impairment.36 Not only pathological studies but also neuroimaging studies have pointed out a role for a cholinergic deficit in cognition in PD. Both PD and PDD have cholinergic neuron decits with vesicular acetylcholine transporter and acetylcholinesterase 37,38 imaging being the decreased VAChT more important and extensive in the cerebral cortex of PDD subjects.39

There are not consistent findings supporting an association between dementia and other monoaminergic systems.

Causes Of Cognitive Impairment In Pd

Cognitive Impairment in Parkinson’s Disease: A Webinar

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.

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Biological Markers Of Cognitive Decline In Genetic Pd

Biomarkers that reflect the pathological processes underlying cognitive dysfunction in PD are still under investigation. The neuropathology underlying dementia in IPD is not well established: several studies demonstrate an association between the presence of cortical Lewy pathology and cognitive decline in PD, but multiple comorbid pathologies can occur in patients with PD and cognitive decline, including cerebrovascular disease, argyrophilic grain disease, hippocampal sclerosis, and Alzheimer’s disease pathology. Significant efforts to identify biomarkers that reflect the presence of proteinopathy and neurodegeneration related to cognitive decline in IPD have been made . Alpha-synuclein levels in CSF were demonstrated to be lower in PD compared with controls but do not seem to differentiate between patients with or without dementia . The results from studies investigating CSF levels of total tau or phosphorylated tau as an indicator of cognitive dysfunction in PD have been inconsistent. However, several studies examining beta-amyloid have found that lower CSF levels of beta-amyloid 142 , the major component of amyloid-b plaques, are associated with worse cognition and that CSF Ab42 levels may predict cognitive decline in PD .

Practical Management Of Pd

Geriatricians are likely to be managing increasing numbers of patients with PD-MCI in the future. Most will not have immediate access to full-neuropsychological assessment in a clinic setting, and it is the authors opinion that the MoCA is the most useful screening tool, with published screening cut-offs for both MCI and PDD , and the advantage of an administration time of just 10 min. Further investigations are generally not required, although a routine dementia screen for reversible causes is warranted. Dopamine agonists for motor control and anticholinergic drugs for non-motor symptoms should be used with caution, or not at all. An explanation to the patient and their family that the prognosis of PD-MCI is uncertain but that in some cases it may be progressive is justified if the patient wishes to know this may prompt further discussion about future advanced care planning.

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Executive Dysfunction In Parkinsons

Executive functions in cognition are higher-order mental processes, including the ability to plan, organize, initiate and regulate behavior to meet goals. Executive functioning is present in activities such as multitasking, switching tasks, and solving problems. The prefrontal cortex of the brain and the dopamine system are responsible for executive function. As PD damages these areas, executive dysfunction occurs, and executive dysfunction is one of the most common cognitive impairments found in people with PD.3,4

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Dementia With Lewy Bodies

Cognitive Impairment and Dementia in Parkinson

Dementia with Lewy bodies is the second most common neurodegenerativedementia. The underlying disease is primarily characterized by alpha-synucleinmisfolding and aggregation within the pathognomonic Lewy bodies, which are alsofound in Parkinsons disease. Onset of symptoms is between the sixth andninth decades, and average survival is 57 years.

With insidious onset and gradual progression, the cognitive deficits aremost prominent in the domains of attention, visuospatial and executive functioning.Additional core features include fluctuating cognition, recurrent visualhallucinations, and parkinsonism.The key distinction between DLB and dementia of Parkinsons disease is basedon the temporal sequence of the cognitive impairment and the movement disorder. InDLB, cognitive impairment precedes the onset of parkinsonism, while in the latter,the cognitive impairment occurs in the context of established Parkinsonsdisease.

Suggestive features of DLB include REM sleep behavior disorder and severeneuroleptic sensitivity. Low dopamine transporter uptake in basal gangliademonstrated by SPECT or PET imaging has been proposed as a suggestive feature.Supportive clinical features include repeated falls and syncope, transient andunexplained loss of consciousness, severe autonomic dysfunction, hallucinations inother modalities, systematized delusions and depression.

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Cognitive Domains And Neurotransmitters

Detailed mechanisms underlying the cognitive impairment in PD are not fully understood. However, it has been well established that PD patients have early cholinergic degeneration in the basal forebrain, which provides cholinergic innervations to the entire neocortex . In addition, the abnormalities in the prefrontal dopaminergic system and other neurotransmitter systems play a role . Pathology in brain regions associated with cognitive functions include Lewy bodies, Lewy neurites, coexistent Alzheimers pathology , and ischemic changes affecting the microvasculature .

How Are Cognitive Changes In Pd Different Than Alzheimers Disease

Overall, dementia produces a greater impact on social and occupational functioning in PD than Alzheimers due to the combination of motor and cognitive impairments.

There is some overlap between symptoms and biological changes seen in Alzheimers and PD. However, it is less likely for both disorders to occur at the same time. Development of dementia in people with PD represents progression of the disease, usually after several years of motor impairment.

Dementia may or may not occur in people with PD. According to recent research, 30% of people with Parkinsons do not develop dementia as part of the disease progression.

  • May be as common as depression in Parkinsons.
  • While less studied, up to 40% of people with PD experience some form of anxiety.
  • Can interfere with memory storage, disrupt attention and complex task performance. For example, most people remember going blank on a school exam when feeling anxious.
  • Negatively impacts social life. People with poorly controlled anxiety often avoid social situations, which can impact family and work relationships.
  • People with PD may experience anticipatory anxiety in situations where they have to use cognitive skills.
  • Similar to depression, successful treatment can lead to improvement of cognitive problems related to anxiety.
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    Causes Of Cognitive Impairment In Parkinsons Disease

    One cause of cognitive changes in patients with Parkinsons disease is a drop in the level of dopamine, the neurotransmitter that is involved in regulating movement as well as cognition, memory and learning, attention, and sleep. However, the cognitive changes associated with dopamine declines are typically mild and circumscribed.

    Other brain changes also are likely involved in cognitive decline in Parkinsons disease. Researchers believe that changes in two other chemical messengers, acetylcholine and norepinephrine, could be linked to memory and executive function loss in Parkinsons disease.

    Vascular Parkinsonism Mimics Array Of Traits

    Thinking Changes in Parkinson’s Disease: Engaging the Nurse

    PORTO, PORTUGAL Vascular parkinsonism displays a range of noncognitive symptoms, which explains why its diagnosis can depend on the bias of the specialist doing the evaluation, said Joseph Ghika, M.D., at the Fourth International Congress on Vascular Dementia.

    The same group of symptoms might be referred to as vascular parkinsonism by movement disorder specialists, central incontinence by urologists, vascular depression by psychiatrists, apraxia of gait by neuropsychologists, gait disorder of hydrocephalus by neurosurgeons, cardiogenic dementia by cardiologists, senile gait disorder by geriatricians, and small- and/or large-vessel disease by stroke specialists, said Dr. Ghika of the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

    Vascular parkinsonism accounts for 3%6% of all Parkinsons disease cases. The evolution of vascular parkinsonism is more rapid than that of PD and may have a stepwise progression. Generally, patients with vascular parkinsonism are older than those with PD and have vascular risk factors. They are usually nonresponsive to dopa treatment.

    Presentation may involve a number of symptoms that are not seen in other forms of cognitive impairment/dementia: gait disturbances , focal deficits, loss of sphincter control, emotional lability , and psychomotor slowing.

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