Pupil-linked arousal, cortical activity, and cognition in Alzheimer’s disease

作者：Michael David, Emma‐Jane Mallas, Lucia M. Li, Magdalena Kolanko, Ramin Nilforooshan, Man Lai Tsoi, Hanim Karakoc, Karen Hoang, Johanna Brandt, Charikleia Triantafyllou, Dragos C. Gruia, Darije Custovic, Peter Lally, Karl Zimmerman, David Sharp, Danielle Wilson, Sarah Daniels, Ramin Nilforooshan, Matthew Harrison, Shlomi Haar, Mara Golemme, Payam Barnaghi, Paul Freemont, Ravi Vaidyanathan, Tim Constandinou, Gregory Scott, Derk-Jan Dijk, Pete Lally, Paresh Malhotra, Louise Robinson, Adam Hampshire, Michael David, Martina Del Giovane, Neil Graham, Magdalena Kolanko, Helen Lai, Lucia M. Li, Mark Crook Rumsey, Emma Jane Mallas, Alina-Irina Serban, Eyal Soreq, Abidemi Otaiku, Megan Parkinson, Thomas Parker, Success Fabusoro, Emily Beal, Alan Bannon, Danilo Mandic, Ziwei Chen, Charalambos Hadjipanayi, Ghena Hammour, Bryan Hsieh, Amir Nassibi, Adrien Rapeaux, Ian Williams, Maowen Yin, Niro Yogendra, Maria Lima, Ting Su, Melanie Jouaiti, Maitreyee Wairagkar, Carlos Sebastian Castillo, Panipat Wattansiri, Thomas Martineau, Mayue Shi, Tianbo Xu, Bo Xiao, Alejandro Valdunciel, Reneira Seeamber, Annika Guez, Zehao Liu, Saksham Dhawan, Nan Fletcher-Lloyd, Samaneh Kouchaki, Alexander Capstick, Chloe Walsh, Louise Rigny, Ruxandra Mihai, Marirena Bafaloukou, Jin Cui, Ann-Kathrin Schalkamp, Yu Chen, Tianyu Cui, Nivedita Bijlani, Michael Crone, Kirsten Jensen, Martin Tran, Thomas Adam, Raphaella Jackson, Alexander Webb, Anne C Skeldon, Kevin Wells, Ullrich Bartsch, Ciro Della Monica, Kiran K G Ravindran, Damion Lambert, Sara Mohammadi Mahvash, Thalia Rodriguez Garcia, Victoria L Revell, Giuseppe Atzori, Lucinda Grainger, Hana Hassanin, James Woolley, Iris Wood-Campar, Janetta Rexha, Sarmad Al Gawwam, Subati Abulikemu, Julian Jeyasingh Jacob, Nathan Steadman, Federico Nardi, Cosima Graef, Alena Kutuzova, Assaf Touboul, Nicolas Calvo Peiro, Jenna Yun, Gaia Frigerio, Adela Desowska, Anastasia Gailly de Taurines, Ruxandra Mihai, Nina Moutonnet, Matthew Harrison, Sophie Horrocks, Brian Quan, Mark Woodbridge, Anna Joffe, Amer Marzuki, Ramsheed Abdul Rahim, Ramin Nilforooshan, Jessica True, Olga Balazikova, Nicole Whitethread, Matthew Purnell, Vaiva Zarombaite, Lucy Copps, Olivia Knight, Gaganpreet Bangar, Sumit Dey, Chelsea Mukonda, Jessica Hine, Luke Mallon, Saijal Jhala, Oliver Sargentoni, Amy Alves, Mahan Heydari, David Wingfield, Claire Norman, Anesha Patel, Ruby Lyall, Sanara Raza, Naomi Hassim, Pippa Kirby, John Patterson, Mike Law, Andy Kenny, Paresh Malhotra, Gregory Scott, David Sharp · 发表于：Brain Communications · 年份：2025 · DOI：10.1093/braincomms/fcaf236 · 被引用次数：9 · 研究领域：Neuroscience, Education and Cognitive Function

Abstract Arousal dysfunction contributes to impairments seen in Alzheimer’s disease. However, the nature and degree of this dysfunction have not been studied in detail. We investigated changes in tonic and phasic arousal using simultaneous pupillometry-EEG, relating these changes to locus coeruleus integrity, a key arousal nucleus. Forty Alzheimer’s disease participants and 30 controls underwent neuropsychological testing using the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), MRI designed to show contrast in the locus coeruleus as a measure of integrity and simultaneous pupillometry-EEG during 5 min of eyes-open resting-state. Pupillometry-EEG was then also applied during an oddball task which included a passive session and sessions in which responses to target stimuli were required, to test the effect of salience. Alzheimer’s disease had lower locus coeruleus integrity (b = −0.26, P = 0.02) and lower peak alpha frequency (tonic arousal) (b = −1.09, P < 0.001). Both were related to ADAS-Cog. There was a very strong relationship between pupil size and both periodic and aperiodic EEG power. Cortical slowing in Alzheimer’s disease affected this relationship, particularly at low frequencies. During the attentionally demanding oddball task, Alzheimer’s disease participants’ behavioural performance was impaired, with reduced accuracy and slower and more variable reaction times. They also had reduced pupil responses to salient stimuli (phasic arousal) (...