Pupillary Responses as a Biomarker of Early Risk for Alzheimer's Disease.
Task-evoked pupillary responses may be a psychophysiological biomarker of early risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Pupil dilation during cognitive tasks reflects cognitive effort until compensatory capacity is surpassed and performance declines are manifest, and reflects activation in the locus coeruleus, where degenerative changes have been found in the earliest stages of AD. We recorded pupillary responses during digit span recall in 918 participants ages 56-66. Despite normal performance, amnestic single-domain MCI (S-MCI) participants showed greater pupil dilation than non-amnestic S-MCI and cognitively normal (CN) participants at lower cognitive loads. Multi-domain MCI (M-MCI) participants failed to modulate effort across cognitive loads and showed poorer performance. Pupillary responses differentiated MCI and CN groups. Amnestic S-MCI participants required compensatory effort to maintain performance, consistent with increased risk for decline. Greater effort in CN individuals might indicate risk for MCI. Results are consistent with dysfunction in locus coeruleus-linked brain systems. This brief task shows promise as a biomarker for early MCI and AD risk prediction.
University of California, San Diego, La Jolla, CA, USA.|VA San Diego Healthcare System, La Jolla, CA, USA.
Eric L
EL
Granholm
University of California, San Diego, La Jolla, CA, USA.
Matthew S
MS
Panizzon
University of California, San Diego, La Jolla, CA, USA.
Jeremy A
JA
Elman
University of California, San Diego, La Jolla, CA, USA.|VA Center of Excellence for Stress and Mental Health, La Jolla, CA, USA.
Amy J
AJ
Jak
University of California, San Diego, La Jolla, CA, USA.|VA Center of Excellence for Stress and Mental Health, La Jolla, CA, USA.
Richard L
RL
Hauger
University of California, San Diego, La Jolla, CA, USA.|VA San Diego Healthcare System, La Jolla, CA, USA.
Mark W
MW
Bondi
Boston University, Boston, MA, USA.
Michael J
MJ
Lyons
University of California, San Diego, La Jolla, CA, USA.
Carol E
CE
Franz
University of California, San Diego, La Jolla, CA, USA.|VA Center of Excellence for Stress and Mental Health, La Jolla, CA, USA.
William S
WS
Kremen
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000175:diagnosis* / Q000503:physiopathology*; D042241:Early Diagnosis; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011939:Mental Recall / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D000075082:Proof of Concept Study; D011680:Pupil / Q000502:physiology; D012306:Risk
Alzheimer’s disease; compensatory cognitive effort; mild cognitive impairment; pupillary responses; pupillometry