Narrative Review of Sensory Changes as a Biomarker for Alzheimer’s Disease

Abstract

Early recognition of Alzheimer’s disease (AD) in the prodromal period has not been robust yet will be necessary if effective disease-modifying drugs are to be useful in preventing or delaying the condition. The objective of this narrative review was to describe the current, evidenced based understanding of alterations in sensory data as potential biomarkers for AD. Review of empirical studies that tested senses as biomarkers for AD and were published in English within the past 50 years was completed. Eighteen empirical studies were identified that met the strict criteria for inclusion, with 12 of these studies being related to the olfactory system. Two studies examined auditory, two examined vision, one examined proprioception, and one examined taste. Thus, only olfaction has been studied to any extent, leaving a clear gap in the literature for the use of other senses. A promising area of research has begun to be reported concerning differences in responses to pain stimuli in AD relative to cognitively normal subjects. Pain is not a single sense like the others but integrates several senses and may allow for use as an early biomarker for AD, as it integrates several brain areas and pathways. Unlike the other senses, simple devices can be used to measure changes in pain perception in cognitively normal adults with genetic predispositions for possible AD, making this potentially useful for clinicians in the future.

Could Altered Evoked Pain Responsiveness Be a Phenotypic Biomarker for Alzheimer’s Disease Risk? A Cross-Sectional Analysis of Cognitively Healthy Individuals

“…Differences observed between APOE4 positive and APOE4 negative cognitively normal individuals in thermal percept detection levels and in pain unpleasantness at each percept may hint at possible mechanisms for how prodromal AD pathology may disrupt pain processing [ 8–11 ]. This possibility is consistent with other work suggesting that alterations in other sensory systems are potential phenotypic markers for subsequent AD risk [ 4 ].…”

“…Carriers of the ɛ 4 allele are at greater risk for amyloid deposition, impacting brain structures such as the hypothalamus and the prefrontal cortex, which may disrupt neural circuits mediating pain perception and behavioral expression that result in differences in psychophysical measurements of pain [ 24, 31, 32 ]. The results of this research demonstrate for the first time that alterations in evoked pain responsiveness may be a potential phenotypic marker for identifying those at risk for APOE4 -related late-onset AD [ 4 ]. In the clinical context, the possibility that APOE4 allele status may alter the risk of pain-related suffering (either by directly increasing pain unpleasantness or delaying necessary medical care due to decreased pain sensitivity) irrespective of AD status may warrant further exploration.…”

“…An initial report of increased neurofibrillary tangles in olfactory bulb in people with AD spurred further studies directly investigating sensory processing in AD [ 3 ]. Since that early report, studies have demonstrated that changes in olfaction, taste, hearing, vision, and proprioception have the potential to serve as biomarkers of AD [ 4 ].…”

“…Sensory processing for all senses (e.g., olfaction, vision, proprioception) involves multisystem physiological mechanisms in which stimuli activate sensory receptors, thereby initiating action potentials leading to central nervous system (CNS) processing and ultimately a perceptual response [ 6 ]. AD-related changes in the CNS have the potential to alter all such sensory processing [ 4 ]. Processing of pain stimuli in the CNS occurs in the lateral (sensory) and medial (emotional) brain networks with the integration of the rostral (behavioral) network in healthy individuals and at varying degrees of neurocognitive impairment, people may present with increased or decreased pain-related behaviors coupled with increased or decreased reports of pain intensity and pain unpleasantness [ 7 ].…”

Brain and Retinal Abnormalities in the 5xFAD Mouse Model of Alzheimer's Disease at Early Stages

“…As early symptoms of AD include functional deficit of smell and vision, olfactory and vision biomarkers are suggested to serve as noninvasive biomarkers to diagnose dementia (Romano et al, 2021). In AD patients or AD mice, beta-amyloid deposition is found in the olfactory bulb [reviewed by Dibattista et al (2020)].…”