Cognitive and Functional Differences Identified in Parkinson Disease Prior to Diagnosis

Kristine Yaffe, MD

Using prospective cohort studies of community-dwelling elders followed up to 20 years, findings published in Neurology identified specific cognitive and functional declines in patients who developed incident Parkinson disease (PD). There were important sex differences as well, as men with incident PD had a steeper decline in executive function compared with women, but only women with incident PD exhibited detectably faster prediagnostic decline in global cognition.

Led by Kristine Yaffe, MD, director of the Center for Population Brain Health at the University of California, San Francisco, the analysis included 9595 women from the Study of Osteoporotic Fractures (SOF) and 5795 men from the Osteoporotic Fractures in Men Study (MrOS). SOF enrolled women aged 65 and over between 1986 and 1988 from 4 sites in the US while MrOS enrolled men aged 65 and older from 2000 to 2002 from 6 sites in the US. Participants underwent 8 evaluations over 20 years of follow-up in SOF, and 12 evaluations over 17 years in MrOS.

A modified version of the Mini-Mental Status Exam (mMMSE) that scores patients 0-26 based on responses, as well as the Trails B, were used to assess cognition in SOF. For MrOS participants, a modified MMSE (3MS) assessed cognition, with scores ranging from 0 (worst cognition) to 100 (best cognition). Trails B was also administered at these time points. In both studies, eligible participants completed an interviewer administered questionnaire on 3 instrumental activities of daily living, and 2 measures of physical function.

Over follow-up, 297 individuals developed incident PD, with outcomes then stratified by sex. While women showed no differences in slopes for global cognition, men with incident PD demonstrated greater prediagnostic decline in this outcome relative to those without PD (–0.04 standard deviation [SD] more annual change; P <.001), which further increased after PD diagnosis (–0.10 SD more annual change; P = .002). Investigators wrote that the differences in global cognition declines “indicates cognitive heterogeneity in the prodromal period by sex.” Notably, men in the study had higher educational attainment but also had increased prevalence of vascular risk factors compared with females.

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Prior to PD diagnosis, women with prediagnostic PD exhibited faster decline in executive function (–0.02 more annual change; P = .006) compared with those without PD; however, there were no between-group differences after diagnosis. As for men, a greater rate of decline in executive function was seen in both the prediagnostic (–0.05 more annual change; P <.001) and post-diagnostic period (–0.20 SD more annual change; P <.001).

Betwene those with and without incident PD, the rates of global cognition decline between at year 5 for men (P <.001) and year 10 for women (P = .022). Among both sexes, the level and rate of decline in executive function started to diverge at year 5 (P <.001 for all), though for women there was no difference at subsequent time points. Sex differences in slopes emerged at 5 years prior to diagnosis for global cognition (P = .006) and 15 years prior to diagnosis for executive function (P = .007).

"A better understanding of the prodromal phase of PD can facilitate symptom management for the many impactful sequelae of early neurodegeneration and recruitment into neuroprotective trials," Yaffe et al wrote. "Future research is needed to further explore the predictive value of combinations of prodromal symptoms and prodromal heterogeneity in other subpopulations."

A sensitivity analysis featuring 163 (55%) individuals who reported physician-diagnosed PD and PD medication use was also conducted. Of 15,092 individuals who did not report PD, 186 (0.01%) reported the use of a PD medication. Despite this, result of the analysis were largely unchanged except for prediagnostic decline in global cognition for men, which became borderline statistically significant (P = .06).

REFERENCES
1. Bock MA, Vittinghoff E, Bahorik AL, Leng Y, Fink H, Yaffe K. Cognitive and functional trajectories in older adults with prediagnostic Parkinson disease. Neurology. Published online December 29, 2022. doi:10.1212/WNL.000000000000206762