Hearing loss and Parkinson’s epilepsy were associated with a future diagnosis of’s disease, an observational study of primary care records in East London showed.
Among ethnically diverse primary care patients, epilepsy (OR 2.5, 95% CI 1.63-3.83) and hearing loss (OR 1.66, 95% CI 1.06-2.58) were linked with a subsequent Parkinson’s diagnosis, reported Alastair Noyce, PhD, of Queen Mary University of London, and co-authors in JAMA Neurology,
Known symptoms associated with Parkinson’s disease, such as tremor and memory problems, were spotted in primary care records years before diagnosis. Tremor was seen up to a decade before (OR 11.66, 95% 6.59–20.64) and memory symptoms emerged 2 to 5 years (OR 3.08, 95% CI 1.81–5.24) before Parkinson’s was diagnosed.
“People see their GPs with symptoms but often don’t get a diagnosis until 5 to 10 years after this,” Noyce said in a statement.
“Tremor, for example, is one of the most recognizable symptoms of Parkinson’s, but was seen 10 years before eventual diagnosis in our study,” he pointed out. “This is too long for patients to wait.”
The primary care setting often is where symptoms that herald the onset of Parkinson’s are first discussed, observed Bhavana Patel, DO, of the University of Florida in Gainesville, and co-authors in an accompanying editorial. “However, little is known regarding the prediagnostic manifestations of Parkinson’s disease that are seen in primary care clinics, particularly in underserved populations,” they wrote.
“As neuroprotective and disease-modifying treatments become available for Parkinson’s disease, early identification and specialist referrals will depend on primary care clinicians,” Patel and colleagues added.
The researchers conducted a nested case-control study using electronic health records from 1990 to February 2018 in primary care practices in East London. In total, 1,055 people with a Parkinson’s diagnosis were matched with 10,550 controls.
In East London, 45% of residents are Black, South Asian, or members of other ethnic groups. Overall, 80% of study participants were from low-income households.
Noyce and co-authors selected 24 exposures based on previous studies of prediagnostic signs and risk factors. “Epilepsy and hearing loss were included given preliminary evidence that these might be prediagnostic features of Parkinson’s disease,” they noted. Three time periods — less than 2 years, 2 to less than 5 years, and 5 to 10 years before diagnosis — were analyzed.
As expected, the researchers identified constipation, fatigue, insomnia, dizziness, cognitive impairment, shoulder pain, and tremor as prediagnostic concerns in the Parkinson’s disease group.
They also found many markers included in prodromal Parkinson’s research criteria: never smoking, type 2 diabetes, parkinsonism, constipation, hypotension or dizziness, erectile dysfunction, depression, anxiety, and global cognitive deficits.
The researchers saw no relationship between ethnicity or economic deprivation and Parkinson’s diagnoses, in contrast to what has been recently reported for dementia.
Epilepsy was associated with subsequent Parkinson’s across all assessed time frames. Hearing loss was associated when identified less than 2 years, or 2 to less than 5 years, before Parkinson’s diagnosis.
“Novel temporal associations were observed for epilepsy and hearing loss with subsequent development of Parkinson’s disease,” Noyce and co-authors noted.
The researchers performed a replication analysis using case-control data from the UK Biobank cohort and found that epilepsy and hearing loss again were associated with subsequent Parkinson’s diagnoses over the three time periods. ORs for epilepsy were about 3 and ORs for hearing loss were approximately 1.2, except for hearing loss in the period closer to Parkinson’s diagnosis (OR 1.03, 95% CI 0.69–1.52).
“There is an emerging literature on auditory processing difficulties in Parkinson’s disease and impaired recognition of musical and nonverbal vocal emotions,” Noyce and colleagues wrote. “Although the role of early hearing loss requires further research, it is possible that this factor represents another deficit in sensory processing that occurs as part of Parkinson’s disease pathogenesis, similar to visual impairment.”
“We believe our findings raise potentially important practical considerations for primary care physicians and the opportunity to address patient concerns at an earlier stage of the disease,” they added. “It is not a case of screening for asymptomatic disease but correctly identifying the underlying cause in patients who are presenting with symptoms and may seek timely onward referral.”
The study had several limitations, the researchers acknowledged. Data were collected from routine primary care records and some signs of Parkinson’s might not have been recorded. Parkinson’s disease may have been misdiagnosed, and information about patient medications, including those that could lead to drug-induced parkinsonism, were not known.
Support for this study came from Barts Charity, Health Data Research UK, and the National Institute for Health Research UCLH Biomedical Research Center.
Noyce disclosed relationships with Parkinson’s UK, Aligning Science Across Parkinson’s, Cure Parkinson’s, Alchemab, Michael J. Fox Foundation, National Institute for Health Research, Barts Charity, uMed, AbbVie, Charco Neurotech, AstraZeneca, Britannia, Biogen, Roche, UCB, and Bial. Co-authors reported relationships with Barts Charity, Biogen, GE Healthcare, MS Society of Great Britain and Northern Ireland, National Multiple Sclerosis Society, BMA Foundation, Horne Family Charitable Trust, Medical Research Council, Roche, Merck, Teva, Novartis, Wolfson Institute of Population Health, and Britannia Pharmaceuticals.
Editorialists reported relationships with the National Institute on Aging, Mangurian-Fixel-McKnight Collaboration for Pilot Studies in Lewy Body Dementia, American Brain Foundation, Mary E. Groff Charitable Trust, Smallwood Foundation, Florida Department of Health, Lewy Body Dementia Association, Alzheimer’s Therapeutic Research Institute, Alzheimer’s Disease Cooperative Study, Parkinson’s Foundation Grant, and the American Academy of Neurology.