Cognitive processes that indirectly affect olfactory dysfunction in Parkinson's disease

Attakias T Mertens,Jonathan B Santo,Katerina Markopoulou,Bruce A Chase

doi:10.1016/j.prdoa.2019.07.003

Attakias T Mertens, Jonathan B Santo + Show 2 more

Open Access

https://doi.org/10.1016/j.prdoa.2019.07.003

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Abstract

IntroductionAccurate early diagnosis of Parkinson's disease is hampered by its long prodromal period and the variable manifestations of its motor symptoms. While olfactory dysfunction can occur before motor-symptom onset and serve as a non-disease-specific diagnostic aid, its underlying causes are incompletely understood. MethodsCorrelation analyses, univariate density estimates, ANOVA and regression evaluated relationships between scores on the Montreal Cognitive Assessment and Hopkins Verbal Learning Test and those on the University of Pennsylvania Smell Identification Test in 1280 Parkinson's Progression Markers Initiative subjects placed into five diagnostic categories. Structural equation modeling identified cognitive measures having significant indirect effects on olfactory-function-test scores. ResultsGlobal cognition, verbal learning and memory, attention, delayed-recall, and visuospatial/executive function scores show weak-to-moderate, significant associations with olfactory-function-test scores. Associations are stronger in symptomatic than asymptomatic subjects having mutations in LRRK2, GBA or SNCA. Score distributions are nonuniform across diagnostic categories. Linear regression found that all cognitive measures except attention predicted olfactory-function-test scores. Three structural equation models assessing indirect effects of verbal learning/memory with either global cognition, visuospatial/executive function, or delayed-recall had a good statistical fit to the data. Only verbal learning/memory scores significantly help explain olfactory-function-test scores in all symptomatic diagnostic categories (−0.56 < b < −0.23, 0.001 < P < .005). Visuospatial/executive-function test scores help explain olfactory-function-test scores in both genetic Parkinson's disease diagnostic categories (−0.25 < b < −0.17, 0.032 < P < .033). ConclusionImpaired verbal learning/memory and visuospatial/executive function contributes to lower performance on olfactory function tests in Parkinson's disease. As both of these domains impact decision-making, decision-making in turn may impact olfactory assessment in Parkinson's disease.

Highlights

Accurate early diagnosis of Parkinson's disease is hampered by its long prodromal period and the variable manifestations of its motor symptoms
We analyzed scores on the University of Pennsylvania Smell Identification Test (UPSIT), a forced-choice test of odor identification [15], the Hopkins Verbal Learning Test (HVLT), an assessment of verbal learning and memory that is a significant predictor of dementia [16,17], and the Montreal Cognitive Assessment (MoCA), which evaluates visuospatial/executive function, attention/concentration, naming, language, immediate and delayed-recall, calculations and orientation, and accurately assesses cognitive impairment in Parkinson's disease (PD) [14,18]
This confirmed previously demonstrated positive associations found in idiopathic PD between scores on the USPIT and tests of verbal learning/memory [12,13], and discovered significant associations between scores on the UPSIT, MoCA, HVLT, Visu-Exec and Delayed-Recall in each symptomatic diagnostic category

Summary

Introduction

Accurate early diagnosis of Parkinson's disease is hampered by its long prodromal period and the variable manifestations of its motor symptoms. Results: Global cognition, verbal learning and memory, attention, delayed-recall, and visuospatial/executive function scores show weak-to-moderate, significant associations with olfactory-function-test scores. Conclusion: Impaired verbal learning/memory and visuospatial/executive function contributes to lower performance on olfactory function tests in Parkinson's disease. Used tests of olfactory function implicitly measure multiple domains, as tests of odor detection, discrimination, and identification require information processing within the olfactory bulb and higher-order associative centers. They may be sensitive to specific types of cognitive impairment, such as memory decline that affects odor-memory retention or the associative processing of an odor memory

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