Olfactory and other sensory impairments in Alzheimer disease

The vast increase in Alzheimer disease (AD) worldwide has grave implications for individuals, family support systems and the health-care systems that will attempt to cope with the disease. Early markers of the disease are essential for efficient selection of clinical trial participants for drug development and for timely treatment once an intervention becomes available. There is avid interest in noninvasive, inexpensive markers that have the potential to identify prodromal AD. This Review considers sensory impairments that have the potential to serve as early indicators of AD, with a focus on olfaction, hearing and vision. Current evidence regarding the potential markers of AD in each modality is examined, with a particular emphasis on olfaction and current findings that olfactory function is associated with prodromal AD. Research suggests that olfactory impairment is associated with other markers that signal the emergence of prodromal AD. Auditory impairment is associated with dementia in epidemiological studies and visual system deficits have been reported in AD; however, the emergence of these deficits in prodromal AD is unclear. Further research is necessary to address the relative sensitivity and specificity of olfactory, auditory and visual measures for the detection of prodromal AD. Early diagnosis of Alzheimer disease (AD) is crucial for efficient selection of clinical trial participants for drug development and ultimately for timely treatment of individuals with AD. Here, Claire Murphy examines the potential for olfactory and other sensory impairments as very early indicators of AD and considers the important questions that remain to be answered. Key points Brain areas involved in olfactory processing — such as the olfactory bulb and entorhinal cortex — show very early neuropathology in Alzheimer disease (AD), suggesting that olfactory function is a potential biomarker. Odour memory and odour identification are profoundly affected in individuals with AD and in those at risk of AD, suggesting that several measures of olfactory function signal preclinical AD. Olfaction currently shows the greatest promise of all sensory biomarkers of AD; odour identification impairment predicts conversion to mild cognitive impairment (MCI) in cognitively normal individuals and conversion to AD in patients with amnestic MCI, and shows substantial relationships with other biomarkers of AD. Epidemiological research indicates that hearing loss at baseline is associated