Summary: Altered pain perception could be a new biomarker to assess late-onset Alzheimer’s risk in cognitively healthy individuals with the AopE4 gene before symptoms occur.
Source: IOS Press
Early diagnosis of Alzheimer’s disease has been shown to reduce cost and improve patient outcomes, but current diagnostic approaches can be invasive and costly. A recent study, published in the Journal of Alzheimer’s Disease, has found a novel way to identify a high potential for developing Alzheimer’s disease before symptoms occur.
Ray Romano, Ph.D., RN, completed the research as part of his Ph.D. in the Nursing Science Program at the University of Tennessee Health Science Center (UTHSC) College of Graduate Health Sciences. Dr. Romano conducted the research through the joint laboratory of Associate Professor Todd Monroe, Ph.D., RN, at The Ohio State University, who is also a graduate of the UTHSC Nursing Science Ph.D. Program and Dr. Ronald Cowan, M.D., Ph.D. who is the Chair of Psychiatry at UTHSC.
Dr. Romano said, “There is a real need to find ways to diagnose Alzheimer’s disease in the primary care setting where most patients first present with concerns for their memory.”
The research found that cognitively healthy people at increased genetic risk of late-onset Alzheimer’s disease showed significantly lower sensitivity to thermal pain but felt greater unpleasantness related to that pain when compared to people at lower risk of the disease.
These results suggest that altered pain perception could potentially be used as a biomarker of late-onset Alzheimer’s disease before symptoms occur.
Previous research had identified a specific genetic allele, APOE4, as a marker associated with an increased incidence of developing late-onset Alzheimer’s disease. In his ground-breaking study, Dr. Romano was able to identify individuals who were cognitively healthy but had the APOE4 allele. He was then able to determine whether people with the APOE4 allele responded differently to experimentally-induced painful stimuli than did cognitively healthy individuals who did not have this allele.
Dr. Cowan noted, “This work also highlights the great strength of joint collaboration between nursing and psychiatry, which have been highly productive for our research programs.” The study included 49 cognitively healthy adults aged 30-89. Twelve of the subjects had the APOE4 allele, and 37 did not. They were assessed for group differences in pain thresholds and feelings of unpleasantness in response to experimentally-induced thermal pain stimuli.
Dr. Romano believes that this is the first report of a connection of APOE4 allele status with an altered response in pain in a cognitively healthy sample of adults across the lifespan.
Use of this biomarker to identify people at risk of Alzheimer’s disease before the onset of serious symptoms would be much less invasive than other methods of Alzheimer’s diagnosis, which include lumbar punctures and positron emission topography (PET) scans. These are expensive tests that are not practical in primary care settings.
“In this exploratory study, Dr. Romano demonstrated that healthy adults with a specific gene for developing late-stage Alzheimer’s disease experience pain differently than people without the genetic marker,” Dr. Monroe said. “Next, we need to examine the brain’s pain systems to determine why this may be occurring. If future studies confirm these results, findings may eventually translate into earlier screening in people at risk of developing Alzheimer’s disease leading to more treatment options.”
Approximately 5.8 million people in the U.S. live with Alzheimer’s disease – the sixth-leading cause of death in the country, according to the Alzheimer’s Association. It is estimated that 500,000 new cases of the disease are diagnosed in the U.S. annually.
About this pain and Alzheimer’s disease research news
Source: IOS Press
Contact: Diana Murray – IOS Press
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Original Research: Open access.
“Could Altered Evoked Pain Responsiveness Be a Phenotypic Biomarker for Alzheimer’s Disease Risk? A Cross-Sectional Analysis of Cognitively Healthy Individuals” by Ray Romano et al. Journal of Alzheimer’s Disease
Could Altered Evoked Pain Responsiveness Be a Phenotypic Biomarker for Alzheimer’s Disease Risk? A Cross-Sectional Analysis of Cognitively Healthy Individuals
This study evaluated whether the apolipoprotein ɛ4 (APOE4) allele, a genetic marker associated with increased risk of developing late-onset Alzheimer’s disease (AD), was associated with differences in evoked pain responsiveness in cognitively healthy subjects.
The aim was to determine whether individuals at increased risk of late-onset AD based on APOE allele genotype differ phenotypically in their response to experimentally-induced painful stimuli compared to those who do not have at least one copy of the ɛ4 allele.
Forty-nine cognitively healthy subjects aged 30–89 years old with the APOE4 allele (n = 12) and without (n = 37) were assessed for group differences in pain thresholds and affective (unpleasantness) responses to experimentally-induced thermal pain stimuli.
Statistically significant main effects of APOE4 status were observed for both the temperature at which three different pain intensity percepts were reached (p = 0.040) and the level of unpleasantness associated with each (p = 0.014). APOE4 positive participants displayed lower overall pain sensitivity than those who were APOE4 negative and also greater overall levels of pain unpleasantness regardless of intensity level.
Cognitively healthy APOE4 carriers at increased risk of late-onset AD demonstrated reduced thermal pain sensitivity but greater unpleasantness to thermal pain stimuli relative to individuals at lower risk of late-onset AD. These results suggest that altered evoked pain perception could potentially be used as a phenotypic biomarker of late-onset AD risk prior to disease onset. Additional studies of this issue may be warranted.