Retinal nerve fibre layer thickness is associated with attention and predicts risk states of dementia

Alzheimer's disease is associated with lower circumpapillary retinal nerve fibre layer thickness (cpRNFLT). It remains unclear if dementia risk states, i.e. mild cognitive impairment (MCI) and mild neurocognitive disorder (NCD) might associate with cpRNFLT and whether specific domains of cognitive function are related. The present study compared systematically all cognitive domains as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) with pointwise analyses of the cpRNFLT and whether cpRNFLT variation can predict MCI and mild NCD. Spectral domain optical coherence tomography scans (768 A-scans of cpRNFLT) were analysed from 1300 participants with reliable measurements, without eye diseases, and further exclusion due to brain disorders. The study was conducted in the framework of the population-based Leipzig Research Centre for Civilization Diseases-(LIFE)-Adult study. The six DSM-5 domains were operationalized by means of both (sub-)scales of the 'Consortium to Establish a Registry for Alzheimer Disease' (CERAD-Plus) neuropsychological test battery and the 'Reading the Mind in the Eyes' test. Age, sex, education and scanning radius were used as additional regressors to adjust for demographics and eye anatomy. 2133 eyes of 1300 subjects were selected (age range 60-79 years). After adjustment for multiple comparisons, in the domain 'attention', worse performance was related to significantly thinner cpRNFL, especially in male participants, most pronounced for temporal and nasal-superior locations. For the domain 'executive function' significantly thicker cpRNFL was found nasally in female participants. There were no significant (P < 0.05) cpRNFLT locations for the DSM-5 domains 'learning/memory', 'perceptual-motor abilities', 'language' and 'social cognition'. Subjects with MCI had thinner cpRNFL temporal-superior compared to subjects with normal cognition. Furthermore, alterations of cpRNFLT in MCI and mild NCD, and subgroups amnestic MCI and amnestic mild NCD existed, for the latter mainly in temporal regions. Compared to cognitively unimpaired, analyses revealed hippocampal volume decreases in MCI and mild NCD groups, and comparable white matter lesion volume, compatible with Alzheimer aetiology. cpRNFL fibre thinning was most prominently associated with lower performance in the attention domain. Highly location specific thinning involved predominantly retinal locations superior and temporal to the optic disc. Thinning in temporal-superior segment was associated with MCI. Temporal thinning indicated amnestic MCI and amnestic mild NCD. Executive function, MCI, and mild NCD presented a concordantly negative association of cognition and RNFLT nasally. As cpRNFLT is obtained conveniently within seconds, our results might assist clinicians by earlier identification of patients at risk for developing cognitive decline associated with diseases like Alzheimer's disease.