Light-Induced Pupillary Responses in Alzheimer's Disease

Chougule, Pratik; Najjar, Raymond P.; Finkelstein, Maxwell T.; Kandiah, Nagaendran; Miléa, Dan

doi:10.3389/fneur.2019.00360

Cited by 86 publications

(88 citation statements)

References 122 publications

(171 reference statements)

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“…In addition to the above reported changes, irregularities in efferent ocular pathways in conjunction with retinal abnormalities were also associated with altered pupillary light response (PLR) in patients. These alterations include increased latency of pupillary constriction to light, decreased constriction amplitude, faster redilation after light offset, decreased maximum constriction velocity and acceleration (Chougule et al, 2019), and altered pupil dilation response during cognitive tasks (Granholm et al, 2017;Kremen et al, 2019). Therefore, there is growing interest in exploring various aspects of pupillary responses, using specialized pupillometry tools, in pre-clinical and clinically diagnosed AD patients.…”

Section: Functional and Visual Changes In Alzheimer's Diseasementioning

confidence: 99%

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

et al. 2020

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The neurosensory retina emerges as a prominent site of Alzheimer's disease (AD) pathology. As a CNS extension of the brain, the neuro retina is easily accessible for noninvasive, high-resolution imaging. Studies have shown that along with cognitive decline, patients with mild cognitive impairment (MCI) and AD often suffer from visual impairments, abnormal electroretinogram patterns, and circadian rhythm disturbances that can, at least in part, be attributed to retinal damage. Over a decade ago, our group identified the main pathological hallmark of AD, amyloid β-protein (Aβ) plaques, in the retina of patients including early-stage clinical cases. Subsequent histological, biochemical and in vivo retinal imaging studies in animal models and in humans corroborated these findings and further revealed other signs of AD neuropathology in the retina. Among these signs, hyperphosphorylated tau, neuronal degeneration, retinal thinning, vascular abnormalities and gliosis were documented. Further, linear correlations between the severity of retinal and brain Aβ concentrations and plaque pathology were described. More recently, extensive retinal pericyte loss along with vascular platelet-derived growth factor receptor-β deficiency were discovered in postmortem retinas of MCI and AD patients. This progressive loss was closely associated with increased retinal vascular amyloidosis and predicted cerebral amyloid angiopathy scores. These studies brought excitement to the field of retinal exploration in AD. Indeed, many questions still remain open, such as queries related to the temporal progression of AD-related pathology in the retina compared to the brain, the relations between retinal and cerebral changes and whether retinal signs can predict cognitive decline. The extent to which AD affects the retina, including the susceptibility of certain topographical regions and cell types, is currently under intense investigation. Advances in retinal amyloid imaging, hyperspectral imaging, optical coherence tomography, and OCT-angiography encourage the use of such modalities to achieve more accurate, patient-and user-friendly, noninvasive detection and monitoring of AD. In this review, we summarize the current status in the field while addressing the many unknowns regarding Alzheimer's retinopathy.

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Section: Functional and Visual Changes In Alzheimer's Diseasementioning

confidence: 99%

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

et al. 2020

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“…1. In the subset of patients in whom pupillometry measurements were performed at days 6 and 7 (n = 30), q-PLR remained significantly lower in patients with delirium (median 22 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] vs. 30 [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43] in non-delirious patients at day 6, and 27 [25][26][27][28][29][30][31] vs. 35 [27][28][29][30][31][32][33][34][35][36][37][38] at day 7; both p < 0.05).…”

Section: Associations Between Icu Delirium and Quantitative Pupillarymentioning

confidence: 99%

“…The pupillary light reflex (PLR) is regulated by the cholinergic system, which mediates pupillary constriction to light stimulation [6]; therefore, quantitative measurement of the pupillary function with automated infrared pupillometry represents an attractive tool for evaluating cholinergic activity in the clinical setting [14][15][16][17][18] and is emerging as a novel monitoring and diagnostic tool in neurological conditions (e.g., Alzheimer's and Parkinson's disease) in which cholinergic deficit is implicated in disease pathogenesis [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Neuromonitoring of delirium with quantitative pupillometry in sedated mechanically ventilated critically ill patients

et al. 2020

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Background: Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. Methods: This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 h. Starting at day 3, automated infrared pupillometry-blinded to ICU caregivers-was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/s). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. Results: A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/s) at day 3, and at all additional time-points tested (p < 0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p = 0.03). Conclusions: Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

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“…Trends over time of q-PLR and CV in delirious vs. non-delirious patients are illustrated in Figure 1. In the subset of patients in whom pupillometry measurements were performed at day 6 and 7 (n=30), q-PLR remained significantly lower in patients with delirium (median 22 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]…”

Section: Associations Between Icu Delirium and Quantitative Pupillarymentioning

confidence: 99%

“…The pupillary light reflex (PLR) is regulated by the cholinergic system, which mediates pupillary constriction to light stimulation [6], therefore quantitative measurement of the pupillary function with automated infrared pupillometry represents an attractive tool for evaluating cholinergic activity in the clinical setting [14][15][16][17][18] and is emerging as a novel monitoring and diagnostic tool in neurological conditions (e.g. Alzheimer's and Parkinson's disease) in which cholinergic deficit is implicated in disease pathogenesis [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Neuromonitoring of delirium with quantitative pupillometry In sedated mechanically ventilated critically ill patients

Favre

Bernini

Morelli

et al. 2020

Preprint

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Background. Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. Methods. This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 hours. Starting at day 3, automated infrared pupillometry – blinded to ICU caregivers – was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/sec). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. Results. A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/sec) at day 3, and at all additional time-points tested ( p <0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p =0.03). Conclusions. Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

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Light-Induced Pupillary Responses in Alzheimer's Disease

Cited by 86 publications

References 122 publications

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

Alzheimer’s Retinopathy: Seeing Disease in the Eyes

Neuromonitoring of delirium with quantitative pupillometry in sedated mechanically ventilated critically ill patients

Neuromonitoring of delirium with quantitative pupillometry In sedated mechanically ventilated critically ill patients

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