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Failing Sense of Smell Linked to Parkinson’s Duration and Progression

smell and Parkinson's

Loss of the sense of smell is associated with longer disease duration in Parkinson’s, suggesting this sense increasingly fails as the disease progresses.

Its decline may be a clinically useful biomarker of Parkinson’s progression and severity, the study’s researchers said.

These findings were in “Association between olfactory impairment and disease severity and duration in Parkinson’s disease,” published in Movement Disorders Clinical Practice.

Loss of smell is a common non-motor symptom of Parkinson’s, and one many patients start experiencing at early disease stages.

Because this symptom often occurs before motor symptoms are evident, testing for the sense of smell has gained interest as a possible way of screening for Parkinson’s early in its course.

But how it progresses as the diseases advances is less known.

Researchers in Japan measured sense of smell in three groups of people: 79 who were recently diagnosed with Parkinson’s (average disease duration, 7.9 months), 71 others with established Parkinson’s (average disease duration, 47.4 months or almost four years), and 128 people without Parkinson’s (controls). The three groups were similar in terms of age (late 70s, on average) and sex (slightly more females than males in all groups).

People with established Parkinson’s had significantly more severe disease, as indicated by higher scores on the Unified Parkinson’s Disease Rating Scale (10.9 vs. 6.3) and lower scores on the Mini-Mental State Exam (26.4 vs. 27.3).

Smell was evaluated using the odor-stick identification test for Japanese (OSIT-J). This test basically involves giving people samples of common smells, like garlic, curry, and menthol, then asking that they identify them. It is scored based on the number of correctly identified smells; the number of indistinguishable smells, meaning the person could smell something, but couldn’t tell what; or samples thought odorless, meaning the person couldn’t smell anything at all.

Compared with controls, those with early and established Parkinson’s had significantly fewer correct answers, as well as significantly more that they couldn’t distinguish among or found odorless.

Recently diagnosed patients had significantly higher average scores for correct smell identification than did those diagnosed years earlier (4.3 vs. 2.5). Newer patients also had significantly fewer smells that were odorless (1.2 vs. 3.8). These differences remained statistically significant after accounting for factors such as disease severity and treatment duration.

Although some previous research has suggested  sex-based differences in smell perceptions, no noteworthy differences in this study were found between men and woman in any group.

“Olfactory dysfunction (fewer correct answers and more ‘odorless’ responses) in both males and females was more severe in PD [Parkinson’s] patients with a previous diagnosis than in patients with recently diagnosed parkinsonism. Thus, olfactory dysfunction [decreased sense of smell] in PD may get worse over time,” the researchers concluded.

Since a longer disease duration was also linked with more severe disease, the researchers noted that a poorer sense of smell was also associated with greater disease severity.

“The assessment of olfactory function is a useful strategy to detect parkinsonism, particularly at the early stage of PD, and it should be more commonly utilized in clinical practice settings as a biomarker of disease progression and severity in PD,” the researchers wrote.

The post Failing Sense of Smell Linked to Parkinson’s Duration and Progression appeared first on Parkinson’s News Today.

Treatments Inadequate for People With Late-stage Disease, Study Says

late-stage Parkinson's

Current Parkinson’s treatments are insufficient for people with late-stage disease, inadequately controlling for many notable motor and non-motor symptoms, a study in these patients across Europe reports.

The study, “The late stage of Parkinson’s — results of a large multinational study on motor and non-motor complications,” was published in Parkinsonism & Related Disorders.

Although therapies like levodopa — its most widely prescribed treatment — effectively manage Parkinson’s symptoms, they tend to lose effectiveness over time. Off periods (times during which symptoms are not controlled by medication) are experienced by about 40% of people diagnosed with Parkinson’s within four to six years, and about 90% of those with a disease duration of more than 10 years.

To better understand how the disease is experienced in the long term, researchers evaluated 692 people with Parkinson’s in six European countries. All were diagnosed at least seven years ago (average disease duration, 15.4 years).

Their daily levodopa dose was a mean equivalence of 874.1 mg.

Falls were the most commonly reported symptom, experienced by 82% of those assessed. This included falls related to freezing (16%), falls unrelated to freezing (21%), and falls both related and unrelated to freezing (45%). Falls were reported as “frequent” by about a quarter (26%) of the people assessed.

Off-periods were present in 68% of these patients, and experienced by 13% for at least half of each day.

Many reported moderate-to-severe severe difficulties in turning in bed (51%), speech (43%), swallowing (16%), and tremor (11%). More than half also reported experiencing fatigue, constipation, urinary symptoms and nocturia (waking up to urinate at night), and problems with concentration and memory.

About a third (37%) of these people had dementia, and 63% experienced hallucinations or delusions, which were severe in 15%.

Long-term levodopa use is known to sometimes cause involuntary movements, referred to as levodopa-induced dyskinesia. Of the people assessed, 45% reported such dyskinesia, though most were mild. In 7%, dyskinesia was moderate to severe.

Another motor problem associated with long-term levodopa treatment is early morning dystonia, or involuntarily muscle clenching. This was reported by 35% of those assessed.

Disability as a whole was most strongly associated with falls, posture problems, bradykinesia (slow movements), cognitive scores, and speech problems.

“These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients,” the researchers concluded.

The post Treatments Inadequate for People With Late-stage Disease, Study Says appeared first on Parkinson’s News Today.

Proposed Parkinson’s Subtypes May Best Capture Disease Stages

proposed Parkinson's subtypes

A proposed system for classifying subtypes of Parkinson’s disease is strongly linked to disease duration and severity, a new study found. This suggests that the system’s proposed subtypes might actually reflect different stages of the disease, rather than distinct clinical subtypes.

The study, “The role of disease duration and severity on novel clinical subtypes of Parkinson disease,” was published in Parkinsonism & Related Disorders.

Parkinson’s progression, as well as its clinical manifestations, varies across patients, suggesting distinct disease subtypes might exist.

Finding different subtypes of Parkinson’s has long been a research goal, as this could allow for more individualized treatment approaches. However, classifying patients into distinct groups that are clinically or biologically meaningful over time has proven a challenge.

A few years  back, a framework was proposed that divides Parkinson’s into three subtypes: mild motor-predominant (MM), diffuse-malignant (DM), and intermediate. These divisions are based on symptoms experienced, particularly motor symptoms, cognitive impairment, rapid eye movement (REM) sleep disorder, and dysautonomia (abnormalities in the autonomic nervous system, which controls involuntary bodily processes like heart rate and sweating).

However, other research has suggested that these subtypes might reflect different stages of the same disease over time, rather than distinct clinical subtypes. The basic idea is that someone early into the disease, and experiencing more mild symptoms, might be classified as mild-motor predominant. But later,  as the disease progresses and symptoms worsen, this same person could be classified as intermediate or diffuse-malignant.

In this study, researchers “aimed to test the influence of disease duration and stage on these novel clinical subtypes” in a group of people with Parkinson’s.

A total of 122 patients (82 males, 40 females; average age, 66.17 ; average disease duration, 5.85 years) were classified according to this system: 49 (40.16%) were included in the mild-motor predominant subtype, 29 (23.78%) in the diffuse-malignant subtype, and 44 (36.06%) in the intermediate subtype.

The researchers compared disease duration — that is, the amount of time since symptoms started — among the three groups. On average, the shortest disease duration was found for the mild-motor predominant subtype (3.75 years), and the longest for the diffuse-malignant subtype (11.04 years), with the intermediate subtype in between (5.11 years).

Subtypes were also examined based on disease duration. Among those with a disease duration of less than five years, 58.34% were classified as mild-motor predominant, compared to 22.58% for those diagnosed 10 or more years ago. For diffuse-malignant, the opposite trend was observed: 5% with a disease duration of less than five years, and 51.61% for 10 years or more.

These subtypes were also associated with those of the Hoehn and Yahr scale (H&Y), which measures disease progression in stages based on severity of symptoms. Broadly, people classified in an earlier stage of disease by H&Y were more likely to be mild-motor predominant than were those classified as having more advanced disease. The opposite was again observed for diffuse-malignant (later stage by H&Y), with the intermediate subtype lying between the two extremes.

Collectively, these data show that the mild-motor predominant, diffuse-malignant, and intermediate subtypes are closely associated with disease duration and stage. This supports the idea that these divisions may actually represent changes in the disease over time, rather than variations person-to-person.

But, the researchers stressed, these findings don’t mean that the subtyping system is wrong, just that its implications need clarification.

“Our results are not in contrast with previous evidence and do not aim to challenge this subtyping system as such, but would call for a clarification of what the construct of subtype should mean,” the researchers wrote.

“Since a patient with MM phenotype at onset will be likely to convert into the DM phenotype at some point, the implication is made that a particular subtype is not able to predict if certain milestones will be reached or not,” they added. “On the other hand, the current data also shows that a proportion of patients have reached the DM stage with short disease duration, which supports the notion that a difference in the rate of progression exists among PD patients.”

The current study’s findings “argue against the concept that these subtypes reflect mutually exclusive disease pathways,” the researchers continued. “The evidence that these subtypes might be not consistent over time has to be taken into account, specifically when attempting to explore correlations with putative biomarkers of disease progression.”

An important caveat of this study is that it was cross-sectional — that is, data were collected at a single point in time, and findings were extrapolated from those data. Further longitudinal studies, which collect data over a length of time, will be needed to validate these findings.

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