Symptom Triad May Identify Parkinson’s Risk

Major Finding: Significantly more individuals with hyposmia had DAT levels of 65% or lower, compared with normosmic individuals (11% vs. 1%).

Data Source: Preliminary findings among 303 participants in PARS.

Disclosures: The study is sponsored by the U.S. Department of Defense, the Michael J. Fox Foundation for Parkinson’s Research, and the National Parkinson Foundation. As an employee of the Institute for Neurodegenerative Disorders, Dr. Marek participates in multiple clinical studies, some of which are funded by drug companies.

BARCELONA – Severe hyposmia may be associated with a deficiency of striatal dopamine transporter protein and slight cognitive decline – characteristics that could identify people with an increased risk of developing Parkinson’s disease, according to preliminary findings from the Parkinson’s Associated Risk Study.

“This is an interesting observation: [Cognitive] decline may be occurring well in advance of motor symptoms,” Dr. Kenneth Marek said at the conference “This might be something we could use to predict who will develop dopamine transporter deficiency and, eventually, symptomatic Parkinson’s.”

The prospective PARS (Parkinson’s Associated Risk Study) aims to test the effectiveness of two biomarkers – sense of smell and dopamine transporter imaging – in identifying subjects who are at risk of developing the disease. First-degree relatives of Parkinson’s disease patients and control subjects will be followed for 2 years to determine whether a deficiency in striatal dopa-mine transporter (DAT) increases their disease risk.

Dr. Marek and his coinvestigators recruited subjects by a mass mailing of the UPSIT (University of Pennsylvania Smell Identification Test); those scoring in the 15th percentile and lower are invited to participate. So far, 9,400 tests have been mailed out, half to relatives of patients and half to subjects recruited by community notices. About 5,000 have sent the test back.

“We have identified 650 people who were hyposmic below this 15th percentile,” said Dr. Marek, president and senior scientist at the Institute for Neurodegenerative Disorders in New Haven, Conn. “This is considered rather severe hyposmia and, interestingly, only about a third of these folks noticed that they even had this symptom.”

He presented data on 303 participants (203 hyposmic, 100 normosmic) who had undergone the baseline evaluation. Tests included a neuropsychological test battery, early Parkinson’s symptom score, and SPECT (single-photon emission CT) brain imaging of striatal DAT binding with the imaging compound iodine-123–beta-CIT. The study is grouping participants according to their striatal DAT levels: Greater than 80% is considered normal, 65%-80% is considered indeterminate, and less than 65% is considered a deficiency consistent with Parkinson’s disease.

Of the 203 hyposmic subjects, 11% had a DAT level less than 65%, compared with 1% of the normosmic group, a significant difference. “That one person in the normosmic group also has a REM sleep behavior disorder,” Dr. Marek noted.

Indeterminate DAT levels were seen in 17% of the hyposmic and in 7% of the normosmic groups, and normal levels were seen in 71% of the hyposmic and 92% of the normosmic groups. (Percentages in the hyposmic group do not equal 100% because of rounding.)

Bowel habits also varied significantly between the groups. Nearly half (48%) of those with the lowest DAT density reported fewer than one bowel movement per day, compared with 21% of the normal-level group. Conversely, 13% of the lowest-level group reported one or more bowel movements per day, compared with 51% of the normal-level group.

“Similarly, [the lowest DAT-level group was] much more likely to endorse questions related to REM sleep behavior disorder,” Dr. Marek said. “And when we used another tool – a nine-item symptom rating scale that assesses early Parkinson’s – those individuals in the lowest DAT group were more likely to endorse the symptoms.”

Taking these data into account, he said it seems as if “these individuals express a number of features that we might call ‘premotor Parkinsonism.’”

The researchers have completed cognitive testing on 131 participants (17 with decreased DAT levels and 114 with normal levels). Mean age was the same (68 years) in both groups and their educational levels were not significantly different.

“Even in this group, [in which all the] subjects were entirely cognitively normal, it was possible to distinguish individuals based on their cognitive function related to whether they had this early DAT deficit or not,” Dr. Marek said. “I would not call them cognitively impaired, because they were not, but they were different and easily distinguished, based on their scores and imaging outcomes.”

Hyposmia, loss of dopamine transporters, and cognitive decline might predict risk for symptomatic Parkinson’s.

Source DR. MAREK

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