The impact of Alzheimer's disease risk factors on the pupillary light response

Alzheimer's disease (AD) is the leading cause of dementia, and its prevalence is increasing and is expected to continue to increase over the next few decades. Because of this, there is an urgent requirement to determine a way to diagnose the disease, and to target interventions to delay and ideally stop the onset of symptoms, specifically those impacting cognition and daily livelihood. The pupillary light response (PLR) is controlled by the sympathetic and parasympathetic branches of the autonomic nervous system, and impairments to the pupillary light response (PLR) have been related to AD. However, most of these studies that assess the PLR occur in patients who have already been diagnosed with AD, rather than those who are at a higher risk for the disease but without a diagnosis. Determining whether the PLR is similarly impaired in subjects before an AD diagnosis is made and before cognitive symptoms of the disease begin, is an important step before using the PLR as a diagnostic tool. Specifically, identifying whether the PLR is impaired in specific at-risk groups, considering both genetic and non-genetic risk factors, is imperative. It is possible that the PLR may be impaired in association with some risk factors but not others, potentially indicating different pathways to neurodegeneration that could be distinguished using PLR. In this work, we review the most common genetic and lifestyle-based risk factors for AD and identify established relationships between these risk factors and the PLR. The evidence here shows that many AD risk factors, including traumatic brain injury, ocular and intracranial hypertension, alcohol consumption, depression, and diabetes, are directly related to changes in the PLR. Other risk factors currently lack sufficient literature to make any conclusions relating directly to the PLR but have shown links to impairments in the parasympathetic nervous system; further research should be conducted in these risk factors and their relation to the PLR.