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Friday, May 24, 2024
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Cognitive Decline Parkinson’s Disease

Other Possible Contributors To Cognitive Decline In Parkinsons

Ask the MD: Cognitive Impairment and Parkinson’s Disease

Hearing is not the only modifiable contributor to cognitive decline. Consider reviewing this list with your doctor to make sure that you do not need to be evaluated for any of these conditions:

Tips and Takeaways

  • Although cognitive decline can be a feature of PD itself, there may be other medical issues that are contributing. Being evaluated for these issues is crucial as modifying them can have a positive impact on cognition and your quality of life.
  • Therefore its very important that you tell your doctor about any changes you notice in your cognitive function so potential corrective action can be taken as early as possible.
  • Hearing loss can be a treatable contributor to cognitive decline. If hearing loss is suspected, consider asking your doctor for a referral for an audiogram. Hearing aids will likely improve your well-being and may improve cognitive decline as well.
  • There are many other treatable contributors to cognitive decline including: medication effects, infection, thyroid abnormalities, low Vitamin B12 levels, strokes, head trauma, orthostatic hypotension, and sleep apnea.

Further Evidence Of Parkinsons Disease Diabetes And Cognitive Decline

Cognitive impairment is a common Parkinsons non-motor symptom, characterized by difficulties that include those of executive function, attention, word finding, and with learning and remembering information.

Other studies show that people using certain anti-diabetes medications are at a lower risk of developing Parkinsons.

Prediabetes, which the scientists note is a high-risk state for diabetes, is also linked in recent studies to faster cognitive decline in dementia-free older adults and to a potential for Parkinsons development. One reason: high levels of glycated hemoglobin in non-diabetic patients are associated with worse motor symptoms, their study noted.

HbA1c is a form of hemoglobin, the protein within red blood cells that carries oxygen, bound to a sugar . HbA1c, or the A1C test, is a standard measure of a persons mean blood glucose level over the preceding two-to-three months, and its used to determine and track diabetes.

However, it remains largely unknown whether prediabetes is related to cognitive impairment in PD, the researchers wrote.

A team at Inha University Hospital, in Incheon, retrospectively analyzed clinical and lab test data from 262 Parkinsons patients followed at their hospital between January 2020 and December 2021.

None of these patients had severe disability, a history of stroke, or severe alterations to the brains white matter, which is composed mainly of nerve fibers.

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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Digging Into The Data On Cognitive Performance

Working as a multidisciplinary team, researchers from infectious disease physicians to neuroscientists analyzed the cognitive performance of 457 people with HIV over two years.

Participants were assessed on a brief cognitive screening test, which evaluated factors such as memory, learning and attention. As well as cognition, the study assessed a broad range of information on psychosocial and socioeconomic determinants of health.

The results revealed that at 12 months and 24 months, only 6% and 7% of people respectively showed significant, or meaningful, cognitive decline. These figures mirror the general population of the same age .

However, over the same intervals, 31% and 25% of participants did show subtle cognitive changes. This mild cognitive decline may be related to small, ongoing changes in the brain among people with HIV, despite having very low levels of HIV in the blood.

The study also found that financial instability, social isolation and severe depression were associated with poorer cognitive health.

Anavex Life Sciences Anavex 2

Cognitive Decline in Parkinson Disease Linked With Alzheimer Genetic ...

Anavex Life Sciences Anavex 2-73/blarcamesine is a sigma-1 receptor agonist which inhibits the release of intracellular calcium into the cytoplasm in part by transferring it to the mitochondria. Aricept/donepezil is also a sigma-1 receptor agonist, although it may preferentially bind to acetylcholinesterases. In any case, at high concentrations Anavex 2-73 vastly outperforms not only a placebo at one year but also donepezil .

At high concentrations in early Alzheimerâs disease and in those with a functioning sigma-1 receptor, Anavex 2-73 led to an average 2 point improvement in Mini-Mental Examination Score at 57 weeks . Four out of six patients improved, one remained at baseline, and one declined in this cohort . At 148 weeks, there was only about a one point mean decline in MMSE scores at high concentrations which would make Anavex 2-73 a disease modifying treatment for Alzheimerâs disease . The change in the Alzheimerâs Disease Cooperative Study-Activities of Daily Living scores was not as dramatic at 57 weeks mostly because there is relatively little change in basic abilities during the early stages of the disease, but the gap grew much larger at 148 weeks.

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Wise Linear Regression Modeling

We modelled a stepwise linear regression analysis in SPSS using the MoCA scores at each of the three different time points as the dependent variable and FBB SUVR values in 20 cortical ROIs at year of scan as the independent variables for both PD and HC separately. This method uses top-down analysis, beginning with all 20 ROIs as potential variables in the model. The algorithm then does multiple regression analyses at once, each time removing the weakest correlated independent variable, in this case an ROI. In the end, only the ROIs that explain MoCA score best are included in a model. The model we presented for each group is the one that maximizes the adjusted R2 value for each year of MoCA score, which means the model that explains the greatest amount of variance in the MoCA score. The adjusted R2 shrinks the R2 with consideration of the number of predictors and sample size in the model . The adjusted R2 can be converted into a percentage value which explains that percentage of the variance. For example, an adjusted R2 of 0.5 would explain 50% of the variance in that model.

The independent variables should be normally distributed, and no relationship should exist between the independent variables . Normality was tested with a Shapiro-Wilks test using SPSS for each ROI found in a regression model. Collinearity was tested with a Durbin-Watson test of collinearity using SPSS .

Acting Out Dreams Predicts Parkinsons And Other Brain Diseases

Enacted dreams could be an early sign of Parkinsons disease

Deena So’Oteh

Alan Alda was running for his life. The actor, best known for his role on the television series M*A*S*H, wasnt on a set. This threat was realor at least it felt that way. So when he saw a bag of potatoes in front of him, he grabbed it and threw it at his attacker. Suddenly, the scene shifted. He was in his bedroom, having lurched out of sleep, and the sack of potatoes was a pillow hed just chucked at his wife.

Acting out dreams marks a disorder that occurs during the rapid eye movement phase of sleep. Called RBD, for REM sleep behavior disorder, it affects an estimated 0.5 to 1.25 percent of the general population and is more commonly reported in older adults, particularly men. Apart from being hazardous to dreamers and their partners, RBD may foreshadow neurodegenerative disease, primarily synucleinopathiesconditions in which the protein -synuclein forms toxic clumps in the brain.

Not all nocturnal behaviors are RBD. Sleepwalking and sleep talking, which occur more often during childhood and adolescence, take place during non-REM sleep. This difference is clearly distinguishable in a sleep laboratory, where clinicians can monitor stages of sleep to see when a person moves. Nor is RBD always associated with a synucleinopathy: it can also be triggered by certain drugs such as antidepressants or caused by other underlying conditions such as narcolepsy or a brain stem tumor.

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Summary Of Vulnerable Cognitive Domains In Pd

Attention: Attention processes are foundational to cognition and interwoven with other cognitive domains, such as memory formulation and orientation. Deficits in this area can substantially affect independence during activities of daily living and are considered by some to be the strongest predictor of caregiver quality of life relative to other cognitive domains . Individuals with PD are reported to have an impaired supervisory attentional system, and consequently show abnormal reliance on cortical executive control for automatic tasks, in addition to the typical non-routine tasks . Thus, persons with PD may tax their executive and attentional processes for all types of tasks, even automatic or routine tasks such as walking and talking . Internal control of attention may also be impaired Dujardin, et al., including tasks requiring sustained and alternating attention . Disruption to attention neural network connectivity, and the associated behavioral manifestations, may be prominent even in mild cognitive impairment from PD .

As with declarative memory, the common approach of assigning implicit memory functions to the basal ganglia and explicit memory functions to the medial temporal lobes has been oversimplified these systems are thought to jointly contribute to behavior, advancing a more integrated view of basal ganglia function and its involvement in memory and learning .

Table 1: Domains of cognition and common methods of measurement. View Table 1

The Era Of Digital Cognitive Testing

September Symposium Series: Cognitive Decline in Parkinson’s

The development of digital cognitive testing and the evolution of self-completed computerized assessments and wearable devices to assess cognitive functioning in daily life, provides an exciting opportunity to both improve clinical management and to obtain more sensitive outcome measures for clinical trials and will likely become a standard procedure in the future, given further technological improvements and increased access to the internet and digital devices. To reach this point, psychometric requirements , documentation and technical problems, as well as their relation to traditional tests, need to be well known.

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How Can Hearing Loss Contribute To Cognitive Decline

It makes sense that hearing trouble can impact cognition. People who do not hear well:

  • do not participate in conversation and limit their social and cognitive engagement, which can contribute to cognitive decline.
  • use more cognitive energy to decipher the sounds that they are hearing. This leaves less cognitive power for other tasks.
  • will have a hard time remembering what they hear.

If those around you tell you that your hearing appears to have diminished, get your hearing evaluated with an audiogram. Improving your hearing with hearing aids could have many positive impacts on your well-being, and potentially improve cognitive functioning as well.

Treatment Of Risk Factors And Comorbidities

There is no disease-modifying therapy for PD, PDD, or DLB however, a recent systemic meta-analysis identified nine risk factors that are associated with increased risk of cognitive impairment in PD . These risk factors include PD-related symptoms , comorbidities , and lifestyles . Importantly, several of these risk factors are potentially modifiable, including alcohol consumption, smoking, and obesity.

Evaluation for cognitive worsening should also include detailed neuroimaging to rule out structural etiologies such as stroke, chronic subdural hematoma, and neoplasm, especially if the cognitive change is abrupt or is associated with other neurological deficits . It is also imperative to check for and treat reversible causes of cognitive impairment such as systemic and central nervous system infections, impaired vision or hearing, metabolic abnormalities , and nutritional deficiencies .

Psychiatric disorders and sleep disorders can themselves provoke and exacerbate cognitive impairment. Therefore, psychiatric disorders, including depression and anxiety, and sleep disorders, in particular obstructive sleep apnea, should be evaluated and treated using a multidisciplinary approach when necessary.

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Future Research And Work With The Community

The study is just a part of the puzzle that is hoping to bring the messaging around cognitive health and people with HIV, particularly in Australia, into sharper focus, Cysique says. She hopes that future research can build on long-term observational studies in people in their 70s and eventually be combined with interventional studies where solutions to manage and improve cognitive and mental health are tested.

Further studies would also need to capture how mild cognitive changes may be affecting people’s ability to perform everyday tasks and their quality of life.

“We want to move towards a holistic care approach for people aging with HIV, one that encompasses cognitive and mental health, and care delivery that is stigma-free. Our group is currently working with researchers, clinicians and HIV community representatives internationally to develop adapted care plans.

“People with HIV have historically been a self-empowered patient group that has contributed to changing the doctor/scientist and patient relationship for the better. Today, clinical research emphasizes the contribution of patient groups in research projects. People with HIV were pioneers in this way, and they continue to advocate for their care as they age.”

More information: Htein Linn Aung et al, Meaningful cognitive decline is uncommon in virally suppressed HIV, but sustained impairment, subtle decline and abnormal cognitive aging are not, eClinicalMedicine . DOI: 10.1016/j.eclinm.2022.101792


Q: What Types Of Improvements Can Be Reasonably Expected From A Course Of Cognitive Rehab

Cognitive Impairment in Parkinson

A: The evidence for cognitive rehab for people with PD is still emerging. It appears that restorative cognitive training can produce short-term improvements in the cognitive skills trained, but the sustainability of those improvements and whether they transfer to improved daily function are not yet known. There are clues that strategy-based approaches that target daily life activities may produce benefits for everyday function, but studies on these approaches are currently limited. Cognitive rehab can also help you figure out how to maintain participation in your existing daily activities and roles and/or find other ways to remain mentally engaged and stimulated throughout your day. A cognitively engaged lifestyle is thought to protect cognition from neurodegeneration and thus may potentially delay or slow cognitive decline associated with PD.

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Identification Of Stimulation Sites: Reprogramming Cohort

As described previously, each subjects electrode position was identified using a patient-specific DBS computer model generated using Cicerone v1.2., Briefly, co-registration between the frame image and a postoperative CT verified the intended surgical placement of the DBS electrode and obtained the final stereotactic coordinates. This was displayed within the model system and volume of tissue activated was computed for each subject before and after reprogramming using the built-in models of Cicerone v1.2. Images were then normalized into ICBM 2009b NLIN asymmetric space based on the local atlas registrations using a self-made MATLAB tool. To avoid any potential for bias in electrode localization or VTA modelling, the VTAs used for our analyses are identical to those used in the initial publication of this dataset.

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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The Picture Of Significant Cognitive Decline So Far

The existing studies in the field of NeuroHIV paint a blurry picture, says Cysique.

Due to inconsistencies in methods and data, there has been contradictory evidence on whether there is a risk of significant cognitive decline in people with HIV. This, in turn, has led to confusing messaging for both the community and clinicians.

“Our study resolves some of the contradictions in the literature and provides a clearer message to doctors and people with HIV,” says Cysique. “And while it clarifies that abrupt cognitive decline is very rare, some people with HIV do remain at risk of cognitive health vulnerabilities that may develop slowly.”

Potential New Medications For Parkinsons Cognitive Decline

Thinking and Memory Problems with Parkinson Disease

With Parkinsons disease , cognitive issues are quite common. Yet, there are currently few medications available to help alleviate this troubling symptom. In the recent past, there were a scarcity of clinical trials testing potential medications for cognitive difficulties and PD. Currently, there is now a long list of potential candidates.To keep in mind: I have not included trials that focus on exercise and rehabilitative techniques or trials that focus on procedures such as deep brain stimulation and their effects on cognition. This list is specifically focused on potential medications.

You may find it helpful to review the types of clinical trials that are typically conducted.

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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


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