Men with nonmotor prodromal symptoms of Parkinson's disease experience cognitive deficits

Men with non-motor characteristics indicative of prodromal Parkinson’s disease exhibited poorer cognitive performance than men without these characteristics, according to cross-sectional study results published in BMJ Neurology Open.

“Subtle cognitive deficits can occur during the prodromal phase of PD, commonly in conjunction with hyposmia. However, little is known about the association between cognitive function and other features suggestive of prodromal PD,” Mario H. Flores-Torres, MD, a PhD candidate in population health science at Harvard University, and colleagues wrote. “We evaluated the association of non-motor prodromal PD features, including hyposmia, constipation and probable REM sleep behavior disorder (pRBD), with objective measures of cognitive function and self-reported cognitive decline.”

Flores-Torres and colleagues used the Health Professionals Follow-Up Study to identify 804 qualifying male participants who responded to telephone-based cognitive interviews between 2016 and 2017. Among the 804 qualifying men, 680 had hyposmia, of whom 45 had PD, while 124 men did not have hyposmia.

The researchers assessed participants’ olfaction, constipation and movement during sleep. They also evaluated objective cognitive function and self-reported subjective cognitive decline to determine the association between the presence of nonmotor features suggestive of prodromal PD and cognitive functioning. They adjusted for age, physical activity, BMI, smoking status and coffee consumption.

The men who displayed nonmotor prodromal features had significantly lower cognitive scores, both objectively and subjectively, than the men with nonmotor features. Also, objective (OR = 7.91) and subjective (OR = 17.42) cognitive impairment occurred more in men with confirmed PD, according to the researchers. Men with hyposmia without other prodromal features performed worse on memory tests. Moreover, those with hyposmia and at least one additional prodromal feature displayed greater impairment in language and verbal fluency and, to a lesser extent, in executive function and memory.

“The combination of hyposmia, constipation and pRBD … has been strongly associated with PD in this cohort, which suggests that men with these features are more likely to be in the prodromal phase of PD rather than AD,” Flores-Torres and colleagues wrote.

They added: “Our study suggests that cognitive impairment is common in individuals with hyposmia, particularly when additional non-motor features of PD, such as constipation and pRBD, are present. The prognostic significance of both subjective and objective measures of cognitive performance and their utility in clinical practice will be determined through longitudinal follow-up currently underway.”

In a related editorial, Peter Kempster, MD, MB, BS, MRCP(UK), FRACP, head of the movement disorders group of neurology and stroke research at Monash University in Australia, discussed the prognostic implications of the study results from Flores-Torres and colleagues, given that the detection of early cognitive deficits may increase the predictive power of the other nonmotor features for the development of PD.

While the study from Flores-Torres and colleagues “broadly replicates” results from other population-based studies, according to Kempster, the researchers’ analysis of prodromal features strengthened the findings. However, he noted that the association must be further explored among younger age groups.

“The findings … suggest that, to a greater degree than has been appreciated, these ‘prodromal’ clinical features also have prognostic significance for cognitive decline and progression to the advanced PD state,” Kempster wrote.