Earlier Onset, Cognitive Impairment and Higher Medication Use Linked to Increased Parkinson’s-related Mortality

Parkinson's mortality studied

Earlier onset of disease, early impairment of memory and thinking, and higher daily use of antiparkinson medication, are associated with increased risk of death related to Parkinson’s disease (PD), according to a study that followed newly diagnosed patients for more than 10 years.

Conversely, being male, the severity of disease symptoms, and general cognitive ability do not seem to contribute significantly to Parkinson’s-related mortality.

The study, “Overall and Disease Related Mortality in Parkinson’s Disease – a Longitudinal Cohort Study,” was published in the Journal of Parkinson’s Disease.

Research has shown that Parkinson’s disease is associated with increased mortality when compared to the general population. However, it remains unclear which factors contribute to this increased mortality and which could be used to predict patients who are at greater risk.

“The reduced life span of patients with PD has been reported earlier, but research on factors associated with this decline has been scarce and of limited scope. While life expectancy is a crude outcome, it is clearly a relevant one, and its association with PD-specific characteristics might help to further understand the heterogeneity of disease often reported in PD,” said Rob M.A. de Bie, MD, PhD, in a press release . De Bie is the study’s senior leader and a neurologist at the University of Amsterdam, Netherlands.

To evaluate potential risk factors for overall and Parkinson’s-related mortality, de Bie and colleagues collected detailed information from a group of 129 newly diagnosed Parkinson’s patients (median age 68.2 years) for at least 13 years, or until death.

This study differed from previous studies because it focused on identifying factors that influenced patients’ mortality related to the disease itself and not just overall mortality.

The median survival of patients after diagnosis was 11.8 years and 85 patients died during the study. The majority of patients were already on levodopa, one of the main medications used to treat the symptoms of Parkinson’s, when they entered the study.

Looking at patients’ characteristics and their survival over time, researchers found that earlier onset of disease, mild cognitive impairment (memory and thinking), and higher daily antiparkinson medication use (measured in levodopa equivalent dose) were all associated with increased death rates related to Parkinson’s.

On the contrary, factors such as male sex, motor symptom severity (as measured by the UPDRS scale), and general cognitive ability (assessed using the Mini-Mental State Examination) did not contribute significantly to the findings.

Higher overall mortality, related or not to Parkinson’s disease, was associated with older age, male sex, greater daily use of antiparkinsonian medications, and mild cognitive impairment.

Despite this study pointing out factors associated with Parkinson’s-related mortality, researchers stressed that due to the observational nature of this data (patients were only followed, with no intervention) it cannot be used to infer cause-effect relationships.

“Therefore, our results do not imply any harm of levodopa treatment,” the researchers wrote. “Theoretically, the most plausible explanation is that progressive disease in terms of motor impairment leads to both early levodopa treatment and increased mortality.”

The team also recommended caution when applying results from population studies such as theirs to individual patients.

“While we found life expectancy in PD to be decreased on average, accurate prediction of individual life expectancy is a more difficult endeavor. Nonetheless, individualized care starts with a better understanding of differences between patients, and our findings show that individual differences in the manifestation of PD are associated with life expectancy,” noted the study’s lead author Jeroen Hoogland, also from the University of Amsterdam.

To provide more accurate predictions of mortality, future research could combine individual patient data with imaging and biomarker-related measures, accompanied by more detailed follow-ups, the team suggested.

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Seize the Moment to Fulfill Your Purpose

Sherri Journeying Through

I lie in bed at night, my left hand under my head. In this position, I can hear the ticking of my watch. Each beat reminds me that another moment no longer exists. I am one second farther from yesterday and one second closer to tomorrow.

About two years ago, a good friend of mine passed away. She lived across the street from me, and we exchanged hellos and see you laters, flower starts, and recipes for homemade cinnamon rolls and minestrone soup. Her cinnamon rolls were out of this world — the best I’ve ever had. 

Then one day, she began to slow down. She didn’t want to do much of anything. Her departure happened suddenly — too suddenly for me. One day I was helping her pull weeds in her side yard, and the next day, it seemed, I was telling her goodbye. That was one of the most surreal moments in my life.

As I stood next to her bedside telling her I’d see her again on the other side, I felt as if I was standing on hallowed ground. It was difficult to put my feet in motion to go home. I wanted to stay and bask in the holiness of that moment.

Another friend who has Parkinson’s lies in her bed now, silently saying her goodbyes to the things of this earth. She no longer wants to go anywhere or do anything. She doesn’t say much to anyone and she can hardly move. My heart aches for her, and just as much for her husband. 

Does her husband know how much she still loves him? Does she know how much he loves her? Do they realize that the days for saying “I love you” are numbered? Have they already passed that moment when there will be no more opportunities for expressing such words?

With the passing of time, opportunities to tell those we love how we feel are frantically fleeting.

We can’t get back what is past and we can’t change the future, nor do we know what it holds. But one thing I do know: I know Who holds my future. 

The other day, I was listening to Steve Harvey, a motivational speaker and the host of “Family Feud.” He was talking about having a purpose in your life. He said that if God is still waking you up in the morning, then He still has something for you to do.

Well, God is still waking me up.

We all have a purpose. Not until we take our final breath have we fulfilled it. Maybe yours is to let your spouse know what a vital role they have played and are still playing in your life with this little monster called Parkinson’s disease. Perhaps it’s to advocate for this disease. Maybe it’s to encourage others who have just begun their race with PD. It could be to bake cinnamon rolls for someone who needs a bright spot in their day.

We aren’t promised tomorrow, but if we wake up, there’s a good possibility it’s for a reason. We may not know what that reason is, which makes it all the more important to seize each moment, before they all tick by.

Encourage someone, love on someone, appreciate someone. Do it now. You might have many days left; they might not. 


Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Nuplazid’s Mortality Risk Not Different from Seroquel, Combo Treatment, Study Finds

Treatment with Nuplazid (pimavanserin) does not lead to a different mortality risk compared to the antipsychotic medication Seroquel (quetiapine), or to combination treatment with both medications, in patients with Parkinson’s psychosis, according to results from a large study.
The study, “Mortality in patients with Parkinson disease psychosis receiving pimavanserin and quetiapine” was published in the journal Neurology.
In April 2016, Acadia Pharmaceuticals’ Nuplazid became the first therapy approved by the U.S. Food and Drug Administration (FDA) for hallucinations and delusions associated with Parkinson’s psychosis.
However, two years later, a CNN report cited an analysis by the nonprofit Institute for Safe Medication Practices, which found a total of 700 deaths in the FDA’s Adverse Event Reporting System — including 500 among Parkinson’s patients in which Nuplazid was the only therapy likely involved — in the nine months following Nuplazid’s arrival on the market in June 2016.
Now, researchers at University of California San Diego School of Medicine explored the medication’s safety further. “We wanted to better understand and assess the risks of using pimavanserin (Nuplazid) within our own patient community, either alone or in combination with other commonly prescribed medications,” Fatta B. Nahab, MD, the study’s senior author, said in a press release.
Besides Nuplazid, the team focused on Seroquel, a second-generation antipsychotic (SGA), which is often used to treat Parkinson’s psychosis. Results were mixed. Use of Seroquel and other SGAs led to concerns about increased morbidity and mortality in patients with dementia or those with Parkinson’s, prompting an FDA black box warning.
Unlike Seroquel, Nuplazid does not affect dopamine receptors, so it does not interfere with the effectiveness of Parkinson’s treatments for motor symptoms.
The team conducted a retrospective analysis of 4,478 UC San Diego Health patients with Parkinson’s, of whom 676 were being prescribed Nuplazid, Seroquel, or both, between April 29, 2016 and April 29, 2018.
Results showed that patients treated with Nuplazid alone (113 patients, mean age 75.9 years) had a lower mortality percentage when compared to those treated with quetiapine only (505 patients, mean age 75.2 years), or with both compounds (58 patients, mean age 74.1 years ). However, the differences were not statistically significant.
When compared to 784 Parkinson’s patients not on these medications (mean age 80 years), the results revealed a significantly greater risk (74%) of mortality in the Seroquel-only group and a trend toward increased risk in the combination treatment group.
“It’s reasonable to assume, however, that individuals requiring these medications have greater disease severity and are at a higher risk of complications and death,” Nahab noted.
A subset of the patients receiving both medications exhibited the highest rate of mortality, although not statistically different. Importantly, the team noted that the combination therapy’s safety is not yet established, as the pivotal Phase 3 trial of Nuplazid (NCT01174004) excluded individuals on antipsychotics.
“Our findings provide the largest comparative report of mortality risk in [Parkinson’s psychosis],” researchers wrote.
However, Nahab noted limitations on the study’s design and nature, which precluded the determination of cause of death or duration of antipsychotic treatment.
“While the results pertaining to [Nuplazid] provide some reassurance for clinicians, patients, and families, future studies

Source: Parkinson's News Today

Higher Mortality Rates Found in Patients with Parkinson’s Dementia, Lewy Body Dementia, Study Shows

higher mortality rates

Patients diagnosed with Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) were found to have a mortality rate more than three times higher than the general population, according to researchers in Sweden.

The 10-year follow-up study, titled “Relative survival in patients with dementia with Lewy bodies and Parkinson’s disease dementia,” was published in the journal PLOS One.

DLB is a neurodegenerative disorder caused by the accumulation of alpha-synuclein protein clumps, leading to physical and cognitive damage.

The alpha-synuclein protein clumps and associated symptoms are also found in a large group of patients with Parkinson’s disease who develop dementia.

Years of research identified a link between the diagnosis of dementia and increased mortality. But the mortality levels greatly depend on dementia type, gender, and study design.

In the general population with dementia, late diagnosis, male gender, the existence of multiple coexisting conditions (comorbidities), and functional disability have been linked to shorter survival.

A research team from Skåne University Hospital in Malmö, Sweden, studied the survival of patients with PDD and DLB compared with the general population. To better understand survival in these groups, the team identified predictors of excessive mortality.

Researchers retrospectively studied 177 patients diagnosed with PDD or DLB from 1997 to 2014 at the Memory Clinic in Malmö. Data collected included demographics, time of first visit, time of diagnosis, comorbidities, apolipoprotein E (APOE) genotyping — a test used to assess a person’s susceptibility for Alzheimer’s disease — and the mini-mental state examination score at the time of diagnosis.

Of the 177 patients included in the study, 131 had DLB, while 46 were diagnosed with PDD. All these patients had at least one comorbidity due to the diagnosis of dementia.

A total of 143 patients (81%) had died by the time of follow-up, with a median survival of 4.1 years.

At a five-year follow-up, the mortality ratio — the ratio between the number of PDD/DLB patients’ deaths over the number of deaths in the general population — was 3.02, and at 10 years, it was 3.44, indicating that PDD and DLB patients have mortality rates more than three times higher than the general population.

Researchers also found that survival was worse if the patients were diagnosed at a younger age, were female, and showed lower scores on the cognitive test.

A more detailed analysis revealed higher mortality in DLB patients who were positive for the APOE test, but not in PDD patients who tested positive in APOE.

This retrospective study demonstrated a higher mortality rate in patients with PDD and DLB compared with the general population 10 years after the diagnosis of the disease.

Also, younger patients, females, and those who tested positive for APOE are linked to excess mortality.

“In conclusion, mortality in patients diagnosed with Lewy bodies and Parkinson’s disease dementia is over three times higher in patients during a ten-year follow-up, compared to persons in the general population unaffected by the disease,” the researchers wrote.

“Excess mortality is found primarily in younger patients, females and carriers of APOE. Further research is required regarding survival and possible interventions, including disease-modifying treatments, to improve care and prognosis for these patients,” they added.

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Source: Parkinson's News Today