Shaun M. Frost, Yogesan Kanagasingam, Hamid R. Sohrabi, Kevin Taddei, Randall Bateman, John Morris, Tammie Benzinger, Alison Goate, Colin L. Masters and Ralph N. Martins Pages 790 - 796 ( 7 )
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. </p> <p> 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. </p> <p> 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. </p> <p> Setting: The pupil response was examined at the McCusker Alzheimer’s Research Foundation in Perth, Western Australia. </p> <p> 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). </p> <p> Main Outcome Measure: Pupil response parameter comparison between mutation carriers and non-carriers. </p> <p> 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%). </p> <p> Conclusions: PFR changes occur pre-symptomatically in autosomal dominant AD mutation carriers, supporting further investigation of PFR for early detection of AD.
Alzheimer’s, autosomal, amyloid, eye, pupil.
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