Enhanced Learning and Memory in Patients with CRB1 Retinopathy

Abstract

Mutations in the CRB1 gene are associated with a diverse spectrum of retinopathies with phenotypic variability causing severe visual impairment. The CRB1 gene has a role in retinal development and is expressed in the cerebral cortex and hippocampus, but its role in cognition has not been described before. This study compares cognitive function in CRB1 retinopathy individuals with subjects with other retinopathies and the normal population.

Methods: Neuropsychological tests of cognitive function were used to test individuals with CRB1 and non-CRB1 retinopathies and compare results with a standardised normative dataset.

Results: CRB1 retinopathy subjects significantly outperformed those with non-CRB1 retinopathy in list learning tasks of immediate (p = 0.001) and delayed memory (p = 0.007), tests of semantic verbal fluency (p = 0.017), verbal IQ digit span subtest (p = 0.037), and estimation test of higher execution function (p = 0.020) but not in the remaining tests of cognitive function (p > 0.05). CRB1 retinopathy subjects scored significantly higher than the normal population in all areas of memory testing (p < 0.05) and overall verbal IQ tests (p = 0.0012). Non-CRB1 retinopathy subjects scored significantly higher than the normal population in story recall, verbal fluency, and overall verbal IQ tests (p = 0.0016).

Conclusions: Subjects with CRB1 retinopathy may have enhanced cognitive function in areas of memory and learning. Further work is required to understand the role of CRB1 in cognition.

Keywords: CRB1; CRB1 retinopathy; blindness; cognitive function; inherited retinal diseases.

Figure 1

Retinal imaging with widefield colour fundus photography, with corresponding fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) of a CRB1-Leber congenital amaurosis (LCA) patient, non-CRB1 LCA, and unaffected control. (A) Thirty-six-year-old female healthy control with 0.00 logMAR vision in each eye, with normal FAF and SD-OCT imaging. (B) Twenty-two-year-old male patient with CRB1-LCA with 1.40 logMAR vision in each eye, displaying widespread nummular pigmentation, dense hypo-AF, and a coarse, thickened retina with retinal disorganisation, with thinning of the outer nuclear layer (ONL) and loss of the ellipsoid zone on SD-OCT imaging. (C) Twenty-eight-year-old female patient with RDH12-LCA, presenting with 1.5 logMAR vision in each eye, displaying bone spicules and macular atrophy, dense hypo-AF, and retinal thinning, including the ONL and loss of the ellipsoid zone on SD-OCT.

Figure 2

(A). Patients with CRB1 retinopathy and non-CRB1 retinopathy exhibited no significant differences in immediate and delayed story recall (p = 0.111 and p = 0.057, respectively). However, both groups displayed significantly higher mean (±SD) scores compared to normal controls in both tasks (* p = 0.0001, ** p = 0.0001). (B). CRB1 retinopathy subjects scored significantly higher than non-CRB1 retinopathy patients (* p = 0.007), and both CRB1 retinopathy and non-CRB1 retinopathy subject mean scores (±SD) were significantly higher than normal controls in the semantic (animal) test (** p = 0.0001, *** p = 0.0001). No significant differences were observed between CRB1 retinopathy and non-CRB1 retinopathy subjects in the phonemic fluency tests (p = 0.363). However, both CRB1 retinopathy and non-CRB1 retinopathy subject mean scores (±SD) were significantly higher than normal controls (* p = 0.0001, ** p = 0.0001). (C). CRB1 retinopathy patients exhibited significantly higher mean (±SD) scores than non-CRB1 retinopathy patients in both the list learning immediate and delayed memory tasks (* p = 0.001 and * p = 0.007, respectively) and normal controls (** p = 0.0001 and ** p = 0.0004, respectively). No significant differences were observed between non-CRB1 retinopathy subjects and normal controls in both tasks (p = 0.6603 and p = 0.8007, respectively) (D). No significant differences were found between CRB1 retinopathy and non-CRB1 retinopathy subjects (p = 0.068) and between CRB1 retinopathy subjects and normal controls in the Hayling test (p = 0.3491). Non-CRB1 retinopathy subjects scored significantly lower than the normal population (* p = 0.0001).

Figure 3

(A). CRB1 retinopathy subjects’ scores were significantly higher compared to non-CRB1 retinopathy subjects in digit span (* p = 0.037), and they outperformed normal controls in digit span (** p = 0.0003) and similarities (** p = 0.002) but not in vocabulary (p = 0.648). Non-CRB1 retinopathy subjects outperformed normal controls in similarities (* p = 0.001) but not in vocabulary (p = 0.3666) or digit span (p = 0.0600) tests. (B). Overall VIQ summary scores showed no significant differences between CRB1 and non-CRB1 subjects (p = 0.142). Both CRB1 (** p = 0.001) and non-CRB1 retinopathy (* p = 0.001) subjects had significantly higher VIQ scores than the normal population. (C). CRB1 retinopathy subjects had significantly lower scores (indicating greater cognitive ability) than non-CRB1 retinopathy patients in the cognitive estimation test (** p = 0.020), while non-CRB1 retinopathy subjects scored significantly higher (indicating lower cognitive ability) than normal controls (* p = 0.004).