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As a result, patients on long-term opioid therapy often experience more pain, even at the same or higher doses of opioids, necessitating further increases in dosage that perpetuate the cycle of hyperalgesia

24 Age-changes in GH secretory dynamics at later stages of life are clinically measurable as frank alterations of the earlier patterns that can be quantified by measurement of pulse timing and amplitude

Furthermore, impaired cerebral metabolism appears to be an early-stage biomarker for ADRD, as several studies have shown reduced glucose metabolism in the hippocampus and posterior cingulate prior to observation of overt clinical symptoms (i.e., cognitive impairment) (Kumar et al., 2022

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