Impaired contrast sensitivity is associated with more severe cognitive impairment in Parkinson disease

https://doi.org/10.1016/j.parkreldis.2016.10.006Get rights and content

Highlights

  • Impaired contrast sensitivity in PD is robustly associated with cognitive deficits.

  • This effect was most significant for executive functions.

  • Findings may have implications for driving safety evaluations in PD.

Abstract

Objectives

Dopaminergic degeneration affects both nigrostriatal projection neurons and retinal amacrine cells in Parkinson disease (PD). Parkinsonian retinopathy is associated with impaired color discrimination and contrast sensitivity. Some prior studies described associations between color discrimination deficits and cognitive deficits in PD, suggesting that contrast discrimination deficits are due, at least in part, to cognitive deficits in PD. We investigated the relationship between cognitive deficits and impaired contrast sensitivity in PD.

Methods

PD subjects, n = 43; 15F/28M; mean age 66.5 ± 8.2, Hoehn and Yahr stage 2.6 ± 0.6, and duration of disease of 6.2 ± 5.0 years underwent neuropsychological and Rabin contrast sensitivity testing.

Results

Mean Rabin contrast sensitivity score was 1.34 ± 0.40. Bivariate analyses showed significant correlation between Rabin contrast sensitivity scores and global cognitive z-scores (R = 0.54, P = 0.0002). Cognitive domain Z-score post hoc analysis demonstrated most robust correlation between Rabin scores and executive functions (R = 0.49, P = 0.0009), followed by verbal learning (R = 0.44, P = 0.0028), visuospatial (R = 0.39, P = 0.001) and attention z-scores (R = 0.32, P = 0.036).

Conclusions

Impaired contrast sensitivity in PD is robustly associated with cognitive deficits, particularly executive function deficits. These results suggest that contrast sensitivity may be a useful biomarker for cognitive changes in PD and may have implications for driving safety evaluations in PD.

Introduction

Parkinson's disease (PD) is a neurodegenerative condition with characteristic motor and non-motor features, including cognitive and visual changes. The latter include impairments in contrast sensitivity and color discrimination [1]. Retinal dopaminergic depletion is well established in PD (parkinsonian retinopathy) [2], [3], [4], [5], [6]. Retinal dopaminergic amacrine cells participate in light adaptation, spatial contrast sensitivity, color discrimination, and photoreceptor renewal [7], [8]. Recent studies using retinal optical coherence tomography showed significant retinal pathologies in PD, including thinning of the retinal nerve fiber layer [9]. While retinal nerve fiber thinning largely reflects retinal ganglia cell pathology, Kaur et al. reported that retinal nerve fiber layer thinning correlated with impaired contrast sensitivity in PD [10]. Another study of retinal nerve fiber layer thickness in PD, however, had a conflicting result [11].

There is evidence to suggest that cerebral deficits may contribute to visual function changes in PD. For example, Bertrand et al. suggested that color discrimination difficulties partially reflect cognitive difficulties, including decreased attention and visuospatial skills, and that color discrimination deficits were associated with the presence of brain white matter microstructural abnormalities [12]. This may also relate to impaired neuronal function in the occipital cortex, which shows decreased glucose metabolism in subjects with PD compared to controls [13]. The combination of mild cognitive impairment (MCI) and visuospatial dysfunctions predicts the development of dementia more so than isolated MCI in PD [14], [15] These observations also imply that some visual function changes share a common neural substrate with processes underlying cognitive impairment in PD, including parallel dopaminergic losses in the retina and the brain in PD [16].

Because of these conflicting observations, it is unclear whether contrast sensitivity is a purely retinal dysfunction or may also reflect central cognitive defects in PD. In the present study, we investigated the relationship between cognitive function and impaired contrast sensitivity in PD.

Section snippets

Subjects and clinical test battery

This cross-sectional study involved analysis of 43 subjects with PD (28 males, 15 females), mean age 66.5 ± 8.2 (range 51–84), mean duration of disease of 6.2 ± 5.0 years (range 0.5–20) and mean Hoehn and Yahr stage 2.6 ± 0.6 (range 1–5). PD subjects met the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria [17]. Subjects on cholinesterase inhibitor drugs were not eligible for the study.

Eighteen subjects were taking a combination of l-DOPA and dopamine agonists, 16 l-DOPA

Results

Mean Rabin contrast sensitivity score was 1.34 ± 0.40 (range 0.6–2.0), mean global cognitive Z-score was −0.44 ± 0.91 (range −3.03 to 0.98). There were 23 subjects with abnormal and 20 subjects with normal range Rabin contrast sensitivity scores. Table 1 shows mean (±SD) values of demographic, clinical, cognitive variables in the patients with PD with abnormal and normal range contrast sensitivity. PD subjects with impaired contrast sensitivity were older and had more severe cognitive

Discussion

We found a significant association between impaired contrast sensitivity and cognitive deficits in PD. Impaired contrast sensitivity most robustly correlated with executive function, verbal learning and visuospatial deficits compared to attention function deficits. These findings extend previous study findings reporting correlation between impaired color discrimination and cognitive deficits in PD [12]. Bertrand et al. however, found that impaired color discrimination most robustly correlated

Disclosures

The authors declare no conflict of interest relevant to this work.

Dr. Ridder has nothing to disclose.

Dr. Muller has research support from the NIH, Michael J. Fox Foundation and the Department of Veteran Affairs.

Dr. Kotagal receives funding from the NIH (P30AG024824 KL2), VA Health Systems (IK2CX001186 and AAVA GRECC), and the Blue Cross & Blue Shield of Michigan Foundation.

Dr. Frey has research support from the NIH, GE Healthcare and AVID Radiopharmaceuticals (Eli Lilly subsidiary). Dr. Frey

Acknowledgements

The authors thank Christine Minderovic, Cyrus Sarosh, Virginia Rogers, the PET technologists, cyclotron operators, and chemists, for their assistance. This work was supported by the Department of Veterans Affairs [grant number grant number I01 RX000317]; the Michael J. Fox Foundation; and the NIH [grant numbers P01 NS015655, P50 NS091856 and RO1 NS070856].

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