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Early signs of Parkinson's disease may emerge 6 years before diagnosis, an analysis of health insurance data showed.

Sensory skin changes, diabetes, and inflammatory conditions were more prevalent in people subsequently diagnosed with Parkinson's compared with controls, as were well-known prodromal features like tremor, reported Anette Schrag, MD, PhD, of University College London in England, and colleagues in

The results validate known Parkinson's risk factors and "confirm some more controversial associations such as with sleep apnea and restless legs syndrome -- which was among the most common early presentations -- and more novel associations such as epilepsy and hearing loss," Schrag told MedPage Today.

Currently, there's high interest in the role of type 2 diabetes and inflammatory conditions in Parkinson's pathogenesis, Schrag pointed out. "Our findings are not only consistent with this but expand on it by including type 1 diabetes and inflammatory bowel disease, also providing further evidence for the hypothesis of early involvement of the gut in many patients," she said.

Prodromal Parkinson's can start more than a decade before diagnosis. To date, the best-established prodromal features are subtle motor symptoms, rapid eye movement sleep behavior disorder, hyposmia or anosmia, neuropsychiatric manifestations, autonomic features, dizziness, fatigue, and pain, Schrag and co-authors noted.

Other research has suggested links between schizophrenia, bipolar disorder, epilepsy, or migraine with subsequent Parkinson's.

Schrag and colleagues evaluated outpatient claims from 138,345 people with incident Parkinson's disease and 276,690 matched controls, using German health insurance records of routine outpatient care from 2011 through 2020. Parkinson's patients had no previous diagnosis of parkinsonism or dementia. Controls were matched on age, sex, region, and earliest year of outpatient encounter.

Participants were tracked for an average of 6 years. In both groups, about 53% were men and the index age was 75. Odds ratios (ORs) were calculated for potential prodromal features of Parkinson's before the index date.

In a novel finding, the researchers determined that diagnoses reflecting changes in skin sensation were tied to a later Parkinson's diagnosis (OR 1.31). Links also emerged with seborrheic dermatitis (OR 1.30) and psoriasis (OR 1.13).

"The early presentation of patients with Parkinson's disease with skin disorders including seborrheic dermatitis, psoriasis, and altered skin sensations may reflect early deposition of alpha-synuclein in skin, inflammatory disposition, and perceptual changes early in the disease process," Schrag said.

Also novel was a relationship with type 1 diabetes (OR 1.32), "which has not been previously reported to be increased in patients with Parkinson's disease or before diagnosis," the researchers wrote. Type 2 diabetes (OR 1.24) was linked to Parkinson's as well.

Epilepsy (OR 2.26) was linked with a later Parkinson's diagnosis, as was hearing loss (OR 1.14), migraine (OR 1.21), and seronegative osteoarthritis (OR 1.21). Gastroesophageal reflux (OR 1.29) and gastritis (OR 1.28) were more prevalent in people who received a subsequent Parkinson's diagnosis.

Consistent with previous reports, risk factors like traumatic brain injury (OR 1.32) and alcohol misuse (OR 1.62) were associated with Parkinson's, while nicotine use had a reduced OR of 0.92.

Up to 10 years before diagnosis, positive relationships were seen between Parkinson's and tremor (OR 4.49), restless legs syndrome (OR 3.73), bipolar disorder (OR 3.80), and schizophrenia (OR 4.00).

The study had limitations: the researchers did not have information about medication, and subtle symptoms and prodromal features were likely to be under-recognized.

"It is also important to note that secondary analysis of claims data is not meant to confirm, but rather to generate, hypotheses on potential associations that can be tested in subsequent primary studies," Schrag and co-authors wrote.

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