Impaired contrast sensitivity is associated with more severe cognitive impairment in Parkinson disease
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].
References (30)
- et al.
Decreased color discrimination and contrast sensitivity in Parkinson's disease
J. Neurol. Sci.
(2000) - et al.
Retinal nerve fiber layer thinning in Parkinson disease
Vis. Res.
(2004) - et al.
Optical coherence tomography as a tool to evaluate retinal changes in Parkinson's disease
Park. Relat. Disord.
(2015) - et al.
Cognitive impairment in patients with Parkinson's disease: diagnosis, biomarkers, and treatment
Lancet Neurol.
(2012) - et al.
Visual contrast sensitivity in Alzheimer's disease, mild cognitive impairment, and older adults with cognitive complaints
Neurobiol. Aging
(2013) - et al.
Correlation of inner retinal thickness evaluated by spectral-domain optical coherence tomography and contrast sensitivity in Parkinson disease
J. Neuro-ophthalmol.: Off. J. North Am. Neuro-Ophthalmol. Soc.
(2013) - et al.
The retina in Parkinson's disease
Brain A J. Neurol.
(2009) - et al.
Visual symptoms in Parkinson's disease and Parkinson's disease dementia. Movement disorders
Off. J. Mov. Disord. Soc.
(2011) - et al.
Retina measurements for diagnosis of Parkinson disease
Retina
(2014) - et al.
Dopamine receptor localization in the mammalian retina
Mol. Neurobiol.
(1999)