In Parkinson’s Disease, Cognitive Symptoms Often Emerge Soon After Diagnosis

About a third of people with Parkinson’s disease reported cognitive symptoms early in the disease course, a large cross-sectional study showed.

Of 25,000 Fox Insight study participants who had a Parkinson’s diagnosis for a median of 3 years, 32% reported at least one cognitive symptom at baseline, reported Jennifer Purks, MD, of the University of Rochester in New York, and co-authors.

The most commonly reported cognitive symptoms involved memory (13%), language or word finding (12%), and concentration or attention (9%), Purks and colleagues wrote in Neurology Clinical Practice.

Cognitive symptoms were reported by 29% of patients in the first year after diagnosis, by 32% in the next few years, and by 35% of patients within 8 to 9 years of diagnosis. These symptoms were predicted by depression (adjusted OR 1.5), worse motor activity scores (OR 1.4 per 10-point increment on a 52-point scale), and higher education (OR 1.2 per year).

In the online Fox Insight study, Parkinson’s patients were asked to report their most bothersome problems in their own words by answering open-ended questions in the Parkinson Disease Patient Report of Problems (PD-PROP). The researchers used human curation, natural language processing, and machine learning to develop an algorithm to convert verbatim responses to classified symptoms.

Subjective cognitive concerns are common in Parkinson’s disease. They don’t always align with objective findings, although a recent Fox Insight study suggested that an estimated 45% of Parkinson’s patients with self-reported cognitive concerns developed new-onset cognition-related functional impairment over 3 years.

“Subjective cognitive complaints may be an early indicator of future decline in cognitive abilities and functional impairment, even when there is currently no evidence of cognitive decline on formal cognitive testing,” observed co-author Daniel Weintraub, MD, of the University of Pennsylvania School of Medicine in Philadelphia.

“Overall, there is alignment between self-reported cognitive decline and objective cognitive assessments, but given how cognitive test norming is done, some high-functioning patients may notice cognitive changes in themselves but test normally,” Weintraub told MedPage Today.

The large sample size of the Fox Insight study, combined with unconstrained free text reporting, allowed the identification of a broader spectrum of bothersome cognitive problems in Parkinson’s than was previously possible, Purks and co-authors pointed out.

“The cognitive concerns begin early after diagnosis and have a parallel association with motor functional impairment and depression,” they noted. “The association of depression with reporting cognitive problems as a most bothersome problem for all domains except visual spatial symptoms demonstrates the importance of mood screening and treatment strategies targeted to the underlying source of the subjective cognitive concerns.”

Purks and colleagues studied data from 25,192 participants in the ongoing Fox Insight study who had a median age of 67. Every 3 months, Parkinson’s patients were asked to respond to the PD-PROP. For people with more than one PD-PROP, only the first report was used.

The researchers also evaluated age, sex, years since diagnosis, and scores on the Movement Disorder Society Unified Parkinson Disease Rating Scale Part II (MDS-UPDRS Part II) and the Geriatric Depression Scale-15 (GDS-15) using Fox Insight data.

The MDS-UPDRS Part II measures motor experiences of daily living; scores range from 0 to 52, with increasing scores indicating greater disability. The maximum interval between PD-PROP data and MDS-UPDRS scores was 90 days. The GDS-15 ranges from 0 to 15, with higher scores indicating more depressive symptoms. Depression was defined by GDS-15 scores of 5 or greater.

A total of 8,001 people reported any cognitive symptom at baseline. Depression was significantly associated with cognitive problems in all domains except visuospatial abilities.

Among Parkinson’s patients with at least one cognitive symptom, 17% reported posterior cortical-related symptoms (visuospatial, memory, or language), 7% reported frontostriatal-related symptoms (executive abilities, concentration, or attention), and 14.3% reported both. The odds of posterior cortical symptoms versus frontostriatal symptoms increased with age and MDS-UPDRS part II scores, but not with depression.

The study had several limitations, the researchers acknowledged. Some patient reports were ambiguous, and misinterpretation or misclassification was possible. Some cognitive categories were broad; more granular classification may have provided additional insights, such as distinguishing language comprehension and expression problems. The online nature of the study also may have led to potential volunteer bias.

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