Visual Performance, Not Retinal Thickness, Better Indicator of Dementia Risk in Parkinson Disease

Rimona Weil, PhD

Recently published findings from a longitudinal study of Parkinson disease (PD) showed that poorer visual performance was a better predictor of dementia than retinal thickness, and thus may be a potential tool for stratification of clinical trials.

The study featured 100 patients with PD and 29 controls who underwent clinical and ophthalmic assessments at baseline, and clinical assessments after approximately 18 and 36 months. At the conclusion of the analysis, visual performance, examined through skew tolerance and biological motion, predicted greater probability of dementia (X² = 5.2; P = .022) and poor outcomes (X² = 10.0; P = .002) than retinal thickness, measured using spectral domain optical coherence tomography (OCT).

Led by Rimona Weil, PhD, consultant neurologist, Dementia Research Center, University College London, higher order visuoperception was measured using tasks probing distinct aspects of higher order visuoperception: the Cats-and-Dogs test and biological motion test. An overall measure of higher order visual function was calculated from the summed z-score of the Cats-and-Dogs and biological motion scores, calculated for each participant with reference for the entire group-average. Retinal layer structure was measured using high-resolution spectral domain OCT, performed on both eyes.

Dividing patients with PD by higher order visual performance, 37 patients were classified as low-vision and 63 as high-vision performers. During follow-up, 14 developed dementia, 4 were too unwell to continue the study, and 2 deaths occurred. When dividing patients according to retinal thickness tertiles, 53 patients were in the low-pfGCIPL group and 48 in the medium/high-pfGCIPL thickness group. Patients in the lowest pfGCIPL thickness tertile were older, with later age of onset versus the medium/high thickness group, and a trend towards having a lower Montreal Cognitive Assessment (MoCA) score.

At the conclusion of the analysis, investigators observed that for every 1-point increase in the higher order vision score, baseline-combined cognition increased by 0.16, adjusted for age (ß = 0.16 [SE, 0.05]; P = .003). There was a significant association between baseline visual performance and MoCA after 36 months (ß = 0.39 [SE, 0.17]; P = .021); however, there were no associations between cognition and other visual measures such as visual acuity and retinal thickness, with the exception of contrast sensitivity, which was positively associated with baseline MoCA (β=3.72 [SE = 1.35]; P = 0.007) and composite cognitive score (β=1.38 [SE = 0.53] P = 0.011) in the PD group but not at 36-month follow-up.

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Weill et al concluded, "Our work provides mechanistic insights into the likely sequence of changes underlying neurodegeneration in PD dementia with earlier higher order visual changes; and shows that visual tests, rather than retinal thickness measures, are likely to be effective and useful for patient stratification in clinical trials."

In patients with PD, worse higher order visual scores significantly predicted lower cognition at baseline and a greater decrease in cognitive score over time, when accounting for baseline cognition. For a 1-unit decrease in the baseline higher order visual score, the combined cognitive score was predicted to decrease by 0.178 (ß = 0.178 [SE, 0.050]; P = .0005) and the decrease per year in cognitive score to be 0.024 points greater (ß = 0.024 [SE, 0.001]; P = .013).

Meanwhile, retinal thickness was not a predictor of differences in the cognitive composite scores at baseline or in the changes of cognitive scores over time in PD (pfGCIPL: ß = –0.013 [SE, 0.080]; P = .87; pfGCPIL time interaction: ß = 0.024 [SE, 0.001]; P = .12). Comparison of the medium/higher and low pfGCIPL tertiles found no association of retinal tertile with risk of dementia (X² = 1.5; P = .22) and a trend towards an association with combined risk of dementia, death, or frailty (X² = 3.4; P = .064).

"For future extensions of this work, longer follow-up duration will be important to further establish the relationship between visual dysfunction, retinal structure and progression to dementia in PD,” the study investigators wrote. "It will be helpful to validate whether simple and accessible forms of visual testing, in larger populations, can robustly predict cognitive change. Finally, pathological confirmation of cortical versus retinal involvement in a prospective cohort would provide definitive evidence for underlying processes driving neurodegeneration in PD."

REFERENCE
1. Hannaway N, Zarkali A, Leyland LA, et al. Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease. Neurol, Neurosurg, and Psych. Published online April 20, 2023. doi:10.1136/jnnp-2023-331083