Context: Alzheimer’s disease (AD) is usually only diagnosed many years after pathology begins. Earlier detection
would allow emerging interventions to have a greater chance to preserve healthy brain function. A rare form of Alzheimer’s
disease, caused by autosomal-dominant mutations, affects carriers with 100% certainty and at a younger age
specific to their mutation. Studying families with these mutations allows a unique investigation of the temporal sequence
of biomarker changes in Alzheimer’s disease.
Objective: To determine whether the pupil flash response (PFR), previously reported to be altered in sporadic Alzheimer’s
disease, is different in pre-symptomatic mutation carriers.
Design: Researchers blinded to participant mutation status collected pupil response data from cognitively normal participants
in the Dominantly Inherited Alzheimer's Network (DIAN) Study during 2010-2011.
Setting: The pupil response was examined at the McCusker Alzheimer’s Research Foundation in Perth, Western Australia.
Participants: Participants were from a single family harboring an Amyloid-Beta Precursor Protein genetic mutation
(APPGlu693Gln). Six carriers and six non-carriers were available for pupil testing (age 43.0±8.3 years old, 2 males and
10 females, 4 with hypertension).
Main Outcome Measure: Pupil response parameter comparison between mutation carriers and non-carriers.
Results: 75% recovery time was longer in mutation carriers (p<0.0003, ROC AUC 1.000, Sensitivity 100%, Specificity
100%) and percentage recovery 3.5 seconds after stimulus was less in mutation carriers (p<0.006, ROC AUC 1.000, Sensitivity
100%, Specificity 100%).
Conclusions: PFR changes occur pre-symptomatically in autosomal dominant AD mutation carriers, supporting further
investigation of PFR for early detection of AD.