Pupillary cholinergic hypersensitivity predicts cognitive decline in community dwelling elders

Previous research demonstrated that it is possible to distinguish patients with probable Alzheimer's disease from age-matched controls based on an exaggerated pupil dilation response to dilute tropicamide. The research reported here employed a prospective longitudinal design to follow over time (2–4 years) a sample of 55 community dwelling elders with and without an exaggerated pupil response using the pupil assay and a comprehensive battery of neuropsychological tests sensitive to pre-clinical AD. Discrete time survival modeling was used to assess the ability of the assay to predict a pattern of cognitive decline consistent with early AD. Analysis showed that there is an increased risk (odds ratio of 3) with a hypersensitive pupil response (≥13% increase in pupil diameter over baseline diameter) for developing significant cognitive impairment in areas of memory attention and language in a pattern, consistent with pre-clinical Alzheimer's disease. When controlling for ApoE allele type the odds ratio for pupil response as a risk factor increased to 4. The analysis also found that an exaggerated pupil response was a significant (p = .02) predictor of cognitive decline. This analysis of longitudinal data has shown that over time an exaggerated response on the pupil assay is a significant independent risk factor for developing pre-clinical Alzheimer's disease. The risk for developing pre-clinical Alzheimer's disease is increased four-fold.