Posts

Subjective Cognitive Decline Could Help Predict Parkinson’s Dementia, Study Contends

cognitive decline

Subjective cognitive decline in Parkinson’s disease could predict the development of dementia. As such, a suitable cognitive screening test could help provide an accurate diagnosis and prognosis.

The study with those findings, “Subjective cognitive decline and progression to dementia in Parkinson’s disease: a long-term follow-up study,” was published in Journal of Neurology.

Even during the early stages of disease, mild cognitive impairment can affect non-demented Parkinson’s patients, and is considered a risk factor for the development of dementia (PDD).

In fact, the prevalence of PDD increases as the disease progresses: from 28% after five years of evolution to 80% after 20 years of the disease.

Subjective cognitive decline — self-reported acquired difficulties with cognitive functioning — is common in the elderly and can be used as a predictor of dementia. In Alzheimer’s disease, subjective cognitive decline has been linked to disease-related tissue/molecular changes and a higher risk for dementia development. However, the predictive value of this type of cognitive status impairment has not been demonstrated yet in Parkinson’s disease.

Scientists from the University of La Laguna, Spain, investigated the neuropsychological profile of subjective cognitive decline in Parkinson’s disease and explored which components could better predict the development of PDD. The team also compared different screening tests to assess subjective cognitive complaints.

A total of 43 Parkinson’s patients and 20 healthy subjects were subjected to neuropsychological examination using a battery of cognitive tests. All patients were being medicated for Parkinson’s and were evaluated during their “on” state — when they are responding to medication and have reduced symptoms.

Subjective cognitive decline was diagnosed using two distinct approaches. A semi-structured interview in which the patient provided his/her subjective opinion on his/her attention, memory, spoken language, naming, written language, visuospatial skills and executive functions; diagnosis was considered when the patient had at least one cognitive complaint. Additionally, a subjective cognitive decline diagnosis also was established on the basis of the interview question concerning memory complaint.

For a mild cognitive impairment diagnosis, investigators followed the criteria proposed by the Movement Disorder Society (MDS)

Based on the results of the interview and on the MDS Task Force criteria, patients were diagnosed as having either subjective cognitive decline or mild cognitive impairment. Of the 43 patients, 13 (30.2%) were diagnosed with subjective cognitive decline, 22 (51.2%) with mild cognitive impairment and 8 (18.6%) had no subjective cognitive complaints. Difficulties in naming and memory were the most frequent cognitive complaints.

Based on memory complaints alone 10 patients (23.25%) were diagnosed with subjective cognitive decline. Interestingly, 10 of the 22 (45.45%) who had been diagnosed with mild cognitive impairment reported no memory complaints.

Mild cognitive impairment subjects performed poorer in the processing speed (the time it takes a person to do a mental task), executive functions (a set of mental skills that helps with organization and regulation), visuospatial skills, memory, and language domains, compared to the other groups.

There were no significant differences between healthy participants (controls)  and Parkinson’s disease patients with subjective cognitive decline in any of the neuropsychological measures.

The team also assessed how many patients diagnosed with subjective cognitive decline progressed to dementia after a mean follow-up of 7.5 years. Fifty percent of mild cognitive impairment patients, 33.3% of individuals diagnosed with subjective cognitive decline, and 14.3% of patients without subjective cognitive complaints developed dementia, which was found to be associated with a poor performance in verbal and visuospatial memory and naming at the beginning of the study.

Additionally, both the language and memory domains were good predictors of dementia development.

“These results are highly relevant for future investigations and also for clinicians: the [subjective cognitive decline] assessment is frequently the first step of cognitive examination and can influence future decisions (e.g., to administer a screening test or a comprehensive neuropsychological assessment),” researchers wrote.

“Assessments that do not include procedures to adequately explore cognitive complaints may underestimate the proportion of [Parkinson’s-related subjective cognitive decline] and, therefore, [mild cognitive impairment] and thus misclassify patients as [Parkinson’s disease] with normal cognition, especially when brief cognitive examinations are chosen,” they concluded.

The post Subjective Cognitive Decline Could Help Predict Parkinson’s Dementia, Study Contends appeared first on Parkinson’s News Today.

Genetic Variant Predetermines Risk of Cognitive Decline in Parkinson’s, Research Suggests

genetic variant

Researchers have found that Parkinson’s patients whose cognitive ability is intact, but who have a specific genetic variant, have significantly less gray matter in the regions of their brain that are related to dementia.

The study with that finding, “Reduced gray matter volume in cognitively preserved COMT 158Val/Val Parkinson’s disease patients and its association with cognitive decline,” was published in Brain Imaging and Behavior.

Several mutations in the COMT gene have been associated with the risk of developing Parkinson’s disease. This gene provides instructions for making catechol-O-methyltransferase (COMT), an enzyme that helps break down certain chemical messengers like dopamine.

The most common alteration in the DNA sequence that makes up the COMT gene is the Val158Met mutation in which a valine (Val) is replaced by a methionine (Met) at position 158. Val and Met are both amino acids, also known as the protein’s building blocks.

Every individual has two copies of each gene, one inherited from each parent. Therefore, a person can have two Val’s in the same position at both COMT gene copies (also known as the Val/Val genotype), a Val in one gene and a Met in the other (Val/Met genotype), or two Met’s (Met/Met genotype). Scientists use the word “genotype” to describe a person’s genetic constitution.

Changes in COMT’s molecular structure, lead to high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzymatic activity.

The Val158Met mutation in the COMT gene has been associated with an increased risk of cognitive decline in Parkinson’s disease, particularly in people with greater COMT activity. When this happens, there is too much neurotransmitter degradation, thus leading to reduced levels of dopamine and affecting basic brain functions such as motor coordination and memory.

Evidence suggests a correlation between cognitive impairment, one of Parkinson’s non-motor features, and reduced gray matter volume.

The brain is composed of gray and white matter. The first consists of cell bodies — the control center of neurons — while the latter is made up of nerve cell projections, known as axons or fibers, connecting distinct parts of gray matter.

A Spanish team of researchers used magnetic resonance imaging (MRI), a non-invasive imaging technology, to investigate a possible structural brain compromise in Parkinson’s patients with highly active COMT activity that could explain their increased risk for subsequent cognitive impairment.

The study included 120 newly diagnosed Parkinson’s patients with normal cognition (who were not previously treated for the disease) and 48 healthy controls from the Parkinson’s Progression Markers Initiative database.

Results showed that there was a widespread, significant reduction in cerebral gray matter volume in patients with the Val/Val genotype. They observed alterations in the fronto-subcortical and posterior-cortical brain regions, where motor and cognitive functions originate.

Gray matter volume at some of the identified regions was associated with cognitive decline in a four-year follow-up period, suggesting that gray matter volume reduction during the early stages of disease predisposes Val/Val patients to cognitive impairment.

Nonetheless, gray matter volume analysis at one-year follow-up was not increased in Val/Val subjects, in comparison to Val/Met and Met/Met participants, indicating a somewhat stable atrophy in the Val/Val subset and that those brain changes might already be present prior to diagnosis.

The team believes their research “sparks the need to further characterize the association between a modified COMT enzymatic effect and a structural brain compromise in the early stages of [Parkinson’s disease].”

The post Genetic Variant Predetermines Risk of Cognitive Decline in Parkinson’s, Research Suggests appeared first on Parkinson’s News Today.

Older IBD Patients Show Increased Risk for Parkinson’s Disease, Study Suggests

IBD risk factor

Older patients with inflammatory bowel disease (IBD) are more likely to develop Parkinson’s disease than those without the condition, a meta-analysis suggests.

Whether the same association exists for younger patients — ages 59 or younger — remains to be determined, according to the researchers.

The study, “Older patients with IBD might have higher risk of Parkinson’s disease,” was published in the journal Gut.

The chronic activation of pro-inflammatory mechanisms, which occurs in autoimmune conditions, has been increasingly recognized as a critical contributor of neurodegenerative disorders.

Studies suggest that this may happen due to the “gut-brain axis” — the two-way communication between the nervous system and the intestine that monitors gut function and links certain regions of the brain to intestinal functions, such as immune activation or intestinal permeability.

In line with the findings, some studies have already reported that patients with IBD — an autoimmune condition characterized by chronic inflammation of the gut — are 22-41% more likely to develop Parkinson’s than those without IBD.

However, a case-control study that examined Medicare data from 89,790 Parkinson’s cases and 118,095 population-based controls suggested that IBD actually reduced the risk for Parkinson’s by 15%.

To clarify this association, a team at Sichuan University in China reviewed all studies investigating the link between IBD and risk of Parkinson’s. Five studies met the inclusion criteria defined by the team, including a total of 9,174,766 participants.

Overall, IBD patients did not have a significantly higher risk of Parkinson’s than reference individuals, nor did patients with ulcerative colitis or Crohn’s disease — the two main forms of IBD — when examined individually.

However, patients 60 years or older were found to have a 32% higher risk of developing Parkinson’s. Patients 50 years or younger did not show this association, the researchers said.

“Our meta-analysis showed that patients with IBD did not have an increased risk of PD; however, subgroup analysis with cohort studies showed that they might be associated with increased risk of PD,” the researchers wrote.

“Age has been regarded as an important risk factor for Parkinson’s disease,” they added, but the findings suggest that “age at IBD diagnosis might be a risk factor of Parkinson’s disease.”

Interestingly, the team found that some studies reported medication-related side effects in the IBD population that resembled parkinsonism in the older population.

“It is necessary to take it into consideration whether older people will take more medications, and whether these medications lead to a higher risk of Parkinson’s also needs further studies to verify in the future,” they said.

Additional well-designed observational studies are still warranted to further explore the risk of Parkinson’s disease within the younger IBD population, the team noted.

The post Older IBD Patients Show Increased Risk for Parkinson’s Disease, Study Suggests appeared first on Parkinson’s News Today.

Mutations on NUS1 Gene Can Significantly Raise Person’s Risk of Parkinson’s, Study Reports

NUS1 mutations

Mutations affecting the NUS1 gene are linked to a significantly increased risk — 11 times higher — of developing Parkinson’s disease, study shows.

The study, “Coding mutations in NUS1 contribute to Parkinson’s disease,” was published in Proceedings of the National Academy of Sciences.

Although exact triggers of Parkinson’s disease remain unclear, aging, and environmental and genetic factors are believed to be major culprits.

SNCA was the first gene to be linked to the development of Parkinson’s. Since its discovery in 1997, scientists have attempted to find other genes that may also play a role.

Chinese researchers conducted a detailed genetic analysis of samples collected from 39 patients with early-onset Parkinson’s disease, their parents, and 20 unaffected siblings, aiming to detect de novo mutations associated with the disease.

A de novo mutation is a genetic alteration evident for the first time in one family member as a result of a mutation in the egg or sperm of a parent, or a mutation that arises in the fertilized egg itself during early development. A child with a de novo (new) mutation will develop the associated disease, while his parents or siblings will not.

Researchers identified 12 genes carrying de novo mutations — MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2. These genes are known to be expressed in two brain regions affected in Parkinson’s disease, called the stratum and substantia nigra, and could be functionally relevant to early-onset Parkinson’s.

Biologic network analysis showed that all the identified genes may share similar biological functions, and act together to increase the risk of developing Parkinson’s.

Patients did not have any other genetic variants previously associated with the disease.

Next, researchers explored the presence of rare mutations in these 12 genes in samples collected from 1,852 patients with sporadic (non-familial) Parkinson’s disease and 1,565 healthy volunteers. In this secondary screening, no significant alterations were found with exception of the NUS1 gene.

To confirm this finding, the team performed a detailed analysis of the NUS1 gene in a larger number of samples (3,237 patients and 2,858 controls). Similar to the previous analysis, Parkinson’s patients carried NUS1 mutations that were not present in the (healthy) control samples.

The presence of NUS1 variants, and consequent lower levels of the gene, were associated with a 11.3 times higher risk of having Parkinson’s disease.

Researchers also examined the role of the NUS1 gene in vivo, by deleting the equivalent gene — which shares 44% similarly with the human NUS1 — in a fly model (Drosophila). They observed that this deletion induced the loss of dopamine-producing nerve cells and, consequently, lower brain dopamine levels — two main hallmarks of Parkinson’s disease.

“These data … suggest that NUS1 plays important roles in dopamine neurons and that the loss of NUS1 could lead to neuronal dysfunction that is related to Parkinson’s disease,” the researchers wrote.

“[D]e novo mutations could contribute to early onset PD [Parkinson’s disease] pathogenesis and identify NUS1 as a candidate gene for PD,” they concluded.

The post Mutations on NUS1 Gene Can Significantly Raise Person’s Risk of Parkinson’s, Study Reports appeared first on Parkinson’s News Today.

Appendix Removal Early in Life Reduces Risk of Developing Parkinson’s, Study Shows

appendix, Parkinson's risk

The healthy human appendix contains Parkinson’s disease-related alpha-synuclein aggregates, and removing the organ early in a person’s life reduces the risk of developing the disease, a study has found.

The study, “The vermiform appendix impacts the risk of developing Parkinson’s disease,” was published in Science Translational Medicine. The work was led by researchers at the Center for Neurodegenerative Science at the Van Andel Research Institute in Michigan.

“Our results point to the appendix as a site of origin for Parkinson’s and provide a path forward for devising new treatment strategies that leverage the gastrointestinal tract’s role in the development of the disease,” Viviane Labrie, PhD, an assistant professor at Van Andel and senior author of the study, said in a press release.

In the brains of Parkinson’s patients, there is a buildup of a protein called alpha-synuclein that forms clumps known as Lewy bodies. These clumps are toxic and lead to neuronal death.

“Gastrointestinal (GI) dysfunction is a common nonmotor symptom of PD [Parkinson’s disease], often preceding the onset of motor symptoms by as many as 20 years,” the researchers wrote.

In addition, it has been shown that neurons innervating the intestines of Parkinson’s patients contain aggregated alpha-synuclein.

“Accumulation of alpha-synuclein in the GI tract not only may contribute to the nonmotor symptoms of PD but also has been hypothesized to contribute to PD pathology in the brain,” the researchers said.

Studies have revealed the existence of many alpha-synuclein aggregates in the appendixes of early-stage and established Parkinson’s patients, as well as in neurologically intact subjects.

The appendix — a worm-like organ that sticks out of the large bowel in the lower right side of the abdomen — helps the immune system detect and eliminate harmful microorganisms, while regulating the gut’s bacterial composition.

In this study, researchers investigated whether this tiny organ contributes to Parkinson’s disease risk.

They analyzed two separate, yet complementary, epidemiological data sets: the nationwide Swedish National Patient Registry (SNPR) and the Parkinson’s Progression Markers Initiative (PPMI).

The SNPR contains information on 1.6 million individuals with a follow-up period of up to 52 years. Investigators identified all individuals who had had an appendectomy (surgical removal of the appendix) from 1964 to 2015 and obtained data on their surgical procedure, year of birth, year of surgical procedure, sex, geographic location (municipality), and, when applicable, date and cause of death. For each patient who underwent an appendectomy, there were two control participants who had not had their appendix removed matched in year of birth, sex, and geographic area.

This data-set analysis revealed that appendix removal was associated with a 19.3% lower risk of developing Parkinson’s than controls. Parkinson’s was diagnosed in 1.17 out of every 1,000 patients who had an appendectomy compared with 1.4 per 1,000 in the general population.

The surgery had the greatest impact on those living in rural areas, with a significant 25.4% reduction in Parkinson’s risk, indicating that removal of the appendix might influence environmental risk factors for the disease. Interestingly, no appendectomy-related benefit was observed in the urban area sample.

“The age of PD diagnosis was, on average, 1.6 years later in individuals who had an appendectomy occurring 20 or more years prior than in cases without an appendectomy. We also observed a significant delay in age of PD onset in individuals with an appendectomy 30 or more years prior, but a limited size in this longer latency group precluded further analysis,” the scientists said.

Researchers then looked at the PPMI data set, which contained detailed information about Parkinson’s diagnosis, age of onset, and other demographic factors, as well as the genetic information of 849 patients.

The team chose to focus on individuals who had their appendix removed at least 30 years before being diagnosed with Parkinson’s, because the early-stage phase of Parkinson’s can last for decades before an accurate diagnosis.

Results showed that age at disease onset was significantly delayed by 3.6 years in those who had undergone an appendectomy (54 individuals, representing 6.4% of the Parkinson’s sample), compared with those who had not.

Disease occurrence was not linked to immune disorders not affecting the gastrointestinal tract, nor was it related to the surgical event itself.

Once a Parkinson’s diagnosis had been established, there were no differences in symptom severity between people with and without a history of appendectomy, suggesting the appendix can potentially impact disease mechanism before the clinical onset of symptoms.

The team then explored the interaction between the appendix and environmental/genetic Parkinson’s risk factors. They reported that the surgical procedure delayed the age of onset in subjects with a family history — meaning those with one or two family members with Parkinson’s — but had no effect in individuals without a family history of the disease.

Importantly, those with a mutation in the LRRK2GBA, or SNCA gene — which are common in hereditary Parkinson’s cases — did not benefit from the appendectomy, indicating that removal of the appendix may be more protective against environmental causes of Parkinson’s rather than genetic ones.

Tissue analysis showed that the mucosa and neurons within the healthy human appendix were filled with aggregated alpha-synuclein. Such accumulation was evident in all age groups, including subjects younger than 20.

Although appendixes of both people with and without Parkinson’s contained disease-prone forms of alpha-synuclein that tend to aggregate rapidly, the Parkinson’s group’s “diseased” protein content was higher than that of the control group.

“We were surprised that pathogenic forms of alpha-synuclein were so pervasive in the appendixes of people both with and without Parkinson’s. It appears that these aggregates — although toxic when in the brain — are quite normal when in the appendix. This clearly suggests their presence alone cannot be the cause of the disease,” Labrie said.

Next, the scientists will search for which appendix-related factor(s) may contribute to Parkinson’s disease.

The post Appendix Removal Early in Life Reduces Risk of Developing Parkinson’s, Study Shows appeared first on Parkinson’s News Today.

High Cholesterol Levels May Protect Against Parkinson’s Disease, Study Suggests

cholesterol, Parkinson's risk

High levels of blood cholesterol may decrease the risk of men developing Parkinson’s disease, according to a large-scale clinical study.

The study, “Higher serum cholesterol and decreased Parkinson’s disease risk: A statin‐free cohort study,” was published in the journal Movement Disorders.

High blood cholesterol, in particular, low-density lipoprotein cholesterol (LDL-C), is a well-established risk factor for coronary disease and stroke. Human and animal studies suggest it may also play a role in the risk of Parkinson’s, although, so far, the data remains controversial.

To explore the association between high cholesterol levels over time and Parkinson’s risk, researchers reviewed the clinical records of 261,638 individuals collected from the medical databases of Maccabi Health Services, the second largest health maintenance organization in Israel.

The study covered all patients, ages 40 to 79, who had undergone at least two cholesterol evaluations between 1999 and 2012 (the study period) and who did not receive statins, which are cholesterol-lowering agents.

During the study period, 746 patients were diagnosed with Parkinson’s disease, 70% of which were definite cases. Disease incidence rates increased with age for both men and women, ranging from 0.06% in men and 0.04% in women at ages 40-44 to 4.8% in men and 3% in women at ages 75-79.

At the beginning of the study, total cholesterol and LDL-C levels were similar among men and women and were slightly higher than optimal standard values. In fact, one-third of the participants had LDL-C levels above 140 mg/dL, the level at which statin therapy is usually recommended, according to clinical guidelines.

Analysis of one-year lagged clinical data revealed that total cholesterol levels greater than 180 mg/dL and LDL-C higher than 110 mg/dL were associated with a reduced risk of Parkinson’s disease in statin-free middle-age men and elderly women.

In men ages 50 to 69, higher total cholesterol levels were associated with an 18-29% reduced risk of Parkinson’s, whereas high LDL-C levels were linked to a 20-28% reduced risk.

In women ages 70 to 74, a similar protective association was reported, but with lower impact. Higher total cholesterol levels were linked to a reduced risk of up to 7%, and high LDL-C levels correlated with a 2-12% reduced risk of Parkinson’s.

“Although our findings could not determine whether decreased cholesterol alone causes PD or whether cholesterol and Parkinson’s disease share a common cause, they strongly imply relevance for clinical practices and health policies,” the researchers wrote.

Additional long-term studies are necessary to “further elucidate the favorable range of cholesterol levels and its changes throughout life that could affect Parkinson’s disease,” they concluded.

The post High Cholesterol Levels May Protect Against Parkinson’s Disease, Study Suggests appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Long Daytime Naps Linked to Higher Risk of Parkinson’s in Older Men in 11-year Study

naps daytime sleepiness

Taking long daytime naps — rather than being excessively sleepy during day hours but not napping — appeared to be linked to a two-times higher risk of Parkinson’s disease in older men in a long-term study.

The study, “Excessive daytime sleepiness, objective napping and 11-year risk of Parkinson’s disease in older men,” was published in the International Journal of Epidemiology.

About half of all Parkinson’s patients report with some form of disturbed sleep and feeling disagreeably sleepy during waking hours. While this is a common non-motor symptom of the disease, it is still unclear if daytime sleepiness could be an early factor — or a risk factor — for Parkinson’s disease.

University of California researchers conducted an 11-year prospective study to understand the association between daytime excessive sleepiness and napping, and the risk of developing Parkinson’s.

They evaluated daytime sleeping patterns in 2,920 men, mean age 76.3 years, who did not have a history of Parkinson’s. Participants reported their sleeping routines and wore a small device on their wrist that objectively recorded their activity and napping habits.

Among the study group, 7.4% of participants reported excessive daytime sleepiness but taking naps for less than one hour during the day. Another 28.1% did not report excessive sleepiness but napped for more than one hour each day.

About 5% reported being both sleepy during daytime hours and taking spending considerable time napping — more one hour each day. These men were found to be older, overweight, showed depressive symptoms, lower cognitive function, and were more likely to have a medical history of stroke, coronary heart disease, hypertension, or diabetes.

The remaining men — 59.5% — reported neither excessive daytime sleepiness nor a habit of daily napping.

During the 11 years of follow-up, 106 of these men were diagnosed with Parkinson’s disease.

Men with excessive daytime sleepiness who also napped for more than one hour a day were 2.52 times more likely to develop Parkinson’s than those who neither took daytime naps or felt extremely sleepy during the day. Men who took long daily naps — but without expressing excessive daytime sleepiness — had a 1.96 increased risk of developing the disease. No link was found between daytime sleepiness alone and Parkinson’s, the study reported.

Rather, longer times spent napping each day, rather than excessive daytime sleepiness, were linked to a higher risk of developing Parkinson’s. “Men with a napping duration of at least 1 h per day were more than twice as likely to develop Parkinson’s compared with those who napped for less than 30 min per day,” the researchers wrote.

Although they lacked information on exactly when a participant developed Parkinson’s, their results suggest that “napping precedes PD diagnosis by at least 2 years,” the researchers wrote.

“Objective measures of napping might be a potentially useful early marker of future risk for Parkinson’s disease,” they added.

Additional studies are needed to further investigate the predictive value of long napping in addition to established risk predictors for the disease, the researchers said.

But they thought their results “might open up new avenues for the early detection of Parkinson’s in the elderly,”  and contributed to treatment strategies that may “be critical for better management of Parkinson’s disease in the long run,” they concluded.

The post Long Daytime Naps Linked to Higher Risk of Parkinson’s in Older Men in 11-year Study appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Better Biomarkers Needed to Diagnose, Predict Risk of Mild Cognitive Impairment

Parkinson's mild cognitive impairment

There still are no reliable biomarkers for early detection, or to characterize and predict risk of dementia, in Parkinson’s disease, according to a recent analysis.

Several studies on the cognitive deficits, progression to dementia, potential biomarkers and the mechanisms underlying Parkinson’s disease mild cognitive impairment (PD-MCI) were analyzed by University College London researchers in the review study “Mild Cognitive Impairment in Parkinson’s Disease—What Is It?,” which was published in the journal Current Neurology and Neuroscience Reports.

Large-scale studies have shown that PD-MCI is not only important, but also common, even at the earliest stages of Parkinson’s disease. In fact, MCI signs can be detected before the onset of Parkinson’s motor symptoms.

About half of Parkinson’s patients with cognitive impairment will progress to dementia in the first 10 years after diagnosis. But considerable variation exists among this patient population regarding the type of cognitive domains affected, the timing, severity and risk of progression to dementia.

Accordingly, PD-MCI is emerging as an intermediate stage between normal cognition and dementia, similarly to the stage of amnestic mild cognitive impairment in Alzheimer’s disease.

Epidemiological studies report that 25 to 50 percent of Parkinson’s patients have MCI, depending on the population and the clinical setting. Identifying individuals with early signs of PD-MCI or at risk of dementia is important to provide early interventions, estimate prognosis, and discover therapeutic targets.

In an effort to clarify the diagnosis of PD-MCI, a task force from the International Parkinson and Movement Disorder Society (MDS) provided a unified definition. According to the new criteria, PD-MCI is defined as an “insidious decline in cognitive abilities reported by patient or informant or observed by the clinician, not caused by other comorbidities.”

Unlike dementia, MCI deficits are detectable, but do not interfere with patients’ autonomy.

The nature and severity of PD-MCI is quite variable. The dominant manifestation does not involve memory. But there are other subtypes with deficits in attention, memory, executive function, psychomotor speed and visuospatial abilities. In some people the deficits can involve multiple cognitive domains.

The MDS has recommended a battery of tests to assess involvement of single or multiple domains and report exactly which domains are affected.

In general, patients with PD-MCI are at higher risk of progressing to dementia than Parkinson patients without MCI. Importantly, studies report that 11 to 28 percent of patients with PD-MCI revert to normal cognition during follow-up.

The variability of these results is likely to reflect differences in study populations, assessment methods and definitions.

Some factors can increase risk of cognitive deficits in Parkinson’s, including being older than 70, akinetic rigid phenotype (freezing and/or falls), poor verbal fluency and higher rates of comorbidities. Higher rates of progression to dementia are associated with older age, depression and a non-tremor clinical manifestations.

Exploring biomarkers

Biomarkers such as amyloid beta protein in the cerebrospinal fluid, and magnetic resonance imaging of the brain, may become important for providing insights into mechanisms of cognitive involvement and for accessing disease progression.

The mechanisms underlying PD-MCI likely involve a combination of factors. Brain aggregates of the proteins alpha synuclein, beta amyloid and tau — the latter two also characteristic of Alzheimer’s disease —  are likely to play a role.

Besides, some studies suggest that changes in specific neurotransmitters — chemical messengers used to communicate between neurons, including acetylcholine, noradrenaline and dopamine — also contribute to cognitive impairment.

Some questions regarding PD-MCI remain unresolved. One of them is the distinction between dementia with Lewy bodies (intracellular accumulations of alpha synuclein) and Parkinson’s dementia.

Dementia with Lewy bodies emerges early, before or within the first year of Parkinsonism, while Parkinson’s dementia is defined as a progressive decline appearing at least one year after motor symptoms are noticeable.

However, given the reports of people with cognitive deficits even before characteristic manifestations of Parkinson’s, perhaps cognitive impairments are the first signs of Parkinson’s disease and may start earlier than believed.

Some studies report that some PD-MCI sub-groups, particularly those with deficits in visuospatial performance, are at the highest risk of dementia.

This underscores the need for better assessment methods and biomarkers of PD-MCI to allow well-defined characterizations of the cognitive deficits and predict who is more prone to dementia.

Although the antipsychotics Nuplazid (pimavanserin) and Clozaril (clozapine) are the only therapies shown to improve Parkinson’s disease psychosis (PDP) symptoms without impairing motor function, there currently are no pharmacological treatments specifically for PD-MCI.

The effect of current experimental therapies on cognition is unknown. Some studies suggest that cognitive training can improve overall cognition in Parkinson’s patients, although the effect seems small.

Physical exercise shows more promising results. Several studies report that moderate intensity aerobic exercises performed two to three times a week lead to some improvement in executive and language functions.

However, Acadia Pharmaceuticals, Nuplazid’s manufacturer, is planning to conduct additional studies of the therapy in PD psychosis patients with a broader range of cognitive abilities and formal cognitive diagnoses, including mild cognitive impairment and dementia.

“Maintaining wide definitions, with poorly differentiated cognitive profiles, prevents accurate comparisons across studies,” researchers wrote. “There is clearly a need for better cognitive phenotyping to enable well-defined sub-groups that are more likely to show similar rates of disease progression.”

“Recognizing the earliest stages of cognitive involvement will allow disease stratification and personalized treatment, with the potential for early intervention. It will enable better-powered clinical trials, and potential outcome measures, ultimately to develop treatments to prevent the progression of dementia in PD,” the review concluded.

The post Better Biomarkers Needed to Diagnose, Predict Risk of Mild Cognitive Impairment appeared first on Parkinson’s News Today.

Source: Parkinson's News Today

Vitamin B12 Supplements May Help Slow Parkinson’s Progression, Study Finds

Vitamin B12 supplement

Low levels of vitamin B12 in patients in the early stages of Parkinson’s disease are linked to faster motor and cognitive decline, suggesting that vitamin supplements may help slow the progression of these symptoms, a study has found.

The study, “Vitamin B12 and homocysteine levels predict different outcomes in early Parkinson’s disease,” was published in the journal Movement Disorders.

Several previous studies have shown that B12 deficiencies are common in Parkinson’s patients. Deficiency of this vitamin promotes development of neurological and motor symptoms associated with the disease, including depression, paranoia, muscular numbness, and weakness.

While most studies have addressed the association of B12 with more advanced Parkinson’s disease, little is known about its contribution in the early stages of the disease before treatment begins.

University of California San Francisco (UCSF) researchers analyzed B12 levels in 680 patients recently diagnosed with Parkinson’s who had not begun treatment. The participants were followed for two years, during which physical and cognitive evaluations were conducted, in addition to B12 assessments. After initial evaluations, the patients were given the option to take a controlled daily multivitamin supplement.

Patients were divided into three groups according to their B12 levels at the beginning of the study. Approximately 13% of the participants had borderline low levels of B12, and 5% had a B12 deficiency. No association was found between low vitamin levels and early motor or cognitive symptoms of Parkinson’s.

The team did find that over time, symptoms in patients with lower B12 levels developed more rapidly than those with higher levels: Patients with lower B12 levels had a significantly reduced ambulatory capacity than patients with higher levels.

“Our findings demonstrate that low B12 levels are associated with greater walking and balance problems, possibly due to the known effect of B12 deficiency on the central and peripheral nervous systems,” Chadwick Christine, MD, UCSF neurologist and lead author of the study, said in a university press release. “Alternatively, low B12 may have a direct effect on the progression of Parkinson’s disease, or it may be a marker of an unknown associated factor, perhaps correlating with another aspect of the disease or nutritional status.”

Subsequent analysis showed improved B12 levels in about 50% of participants, indicating they had chosen to take the multivitamin supplement. Disease progression in this group of patients was found to be much slower, based on the annualized average increase of disability on the Unified Parkinson’s Disease Rating Scale (UPDRS) score  — a measure of Parkinson’s disability. Patients with improved B12 levels had an increase to only 10.11 on the scale, showing less disability, compared with 14.38 in patients who maintained low B12 levels throughout the study.

The team also evaluated the blood levels of homocysteine, an amino acid that is usually elevated in people with low B12 levels. There was a significant association between high levels of homocysteine — thus lower B12 — and faster cognitive decline.

“Our results suggest that the measurement of B12 levels early in Parkinson’s may be beneficial,” Christine said. “If levels are at the low end of normal, supplementation to get the level into the middle or upper end of the normal range may slow development of symptoms.”

Further studies are warranted to shed light on how vitamin B12 might benefit Parkinson’s patients, and to fully address its therapeutic potential on disease progression.

The study was supported by funding from the Michael J. Fox Foundation, and gifts from the Ko and Tsu family and William and Mary Ann S. Margaretten.

The post Vitamin B12 Supplements May Help Slow Parkinson’s Progression, Study Finds appeared first on Parkinson’s News Today.

Source: Parkinson's News Today