The pupil light reflex (PLR) for focal chromatic stimuli was tested in 125 healthy middle-aged subjects offspring of Alzheimer Disease (AD) patients and 61 age-matched controls,. Machine learning algorithms identified features associated with PLR latency with an Area Under Curve of 0.91±0.05 in the left eye and 0.88 ± 0.05 in the right eye. Parameters associated with the contraction arm of the PLR were more discriminative compared to parameters associated with the relaxation arm. This study suggests that subtle changes in pupil constriction latency may be detected decades before the onset of AD clinical symptoms using a simple, non-invasive chromatic pupilloperimetry test.
Purpose: To identify early retinal biomarkers for Alzheimer disease (AD) using multimodal imaging.
Methods: Infra-red (IR) and multicolor fundus imaging and spectral domain optic coherence tomography (SD-OCT) were performed in 108 offspring of AD patients (FH+) and 44 age-matched controls (FH-). All subjects were tested for cognitive function by executive function and episodic memory tests. MRI brain imaging was performed on a 3T MRI.
Results: In FH+ subjects, lower performance in memory was associated with thicker peri-papillary temporal-superior RNFL (r=-0.220; p=.016). In FH- subjects, the correlation was in the opposite direction (r=0.335; p=.013). In FH+, left Hippocampal volume was associated with larger total macular thickness (r=0.212; p=.028), as well as thicker macular RNFL (r=0.216; p=.025), macular GCL (r=0.221; p=.022), and macular IPL (r=0.285, p=.003). Similar results were found in the right eye.
Conclusions: The thickness of inner retinal layers and peripapillary RNFL are associated with cognitive functioning and hippocampal volume in asymptomatic subjects at high risk for AD and may present novel biomarkers for very early detection of AD.
The pupil responses of 15 cognitively normal subjects (ages 60-74) were examined in response to 76 focal red and blue light stimuli using a chromatic multifocal pupillometer (CMP). Subjects with low cognitive scores as determined as by Montreal Cognitive Assessment testing, presented significantly weaker and sluggish pupil responses in peripheral and central locations of the visual field in response to red and blue light. Our findings suggests that the CMP may present a novel objective, non-invasive, low cost technique for early diagnosis of cognitive decline that may serve for Alzheimer Disease prevention and as sensitive outcome measure of therapeutic effects.
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