The prefrontal cortex is the most age-vulnerable region of the human brain, losing approximately 5%of gray matter volume per decade from early adulthood, with concurrent age-related decline indopaminergic and noradrenergic neurotransmission. In a clinically significant subset of older adults,these changes produce emotional dysregulation, impaired inhibitory control, and social behavioraldisturbance that generate caregiver burden and social isolation — yet no diagnostic category inDSM-5 or ICD-11 captures this condition when dementia and major depression have been excluded.We propose Age-Related Prefrontal Emotional Dysregulation (ARPED) as a definable medical entitywarranting pharmacological intervention. The neurobiological basis of ARPED convergesmechanistically with attention deficit hyperactivity disorder: both conditions involve insufficientcatecholamine stimulation of prefrontal circuits, producing overlapping deficits in executive controland emotional regulation through the same inverted U dose-response curve. The etiologies differ —neurodevelopmental genetics versus age-related neurodegeneration — but the functional endpoint isequivalent. We demonstrate that the DSM-5 definition of a mental disorder, applied consistently,logically requires recognition of ARPED; its current exclusion reflects a logical inconsistency inwhich "naturalness" of etiology is invoked to deny treatment for age-related frontal dysfunctionwhile identical reasoning is not applied to ADHD or depression. We propose methylphenidate andvenlafaxine as first-line candidates for clinical investigation, based on their demonstrated efficacy foremotional dysregulation in ADHD and for executive function in geriatric depression, respectively.We present five testable predictions and a proposed randomized controlled trial design. In an erawhen multiple OECD nations have abolished mandatory retirement and aging societies increasinglydepend on mutual aid among those with extended healthy lifespans, the inability to treat age-relatedfrontal dysfunction represents not only a clinical failure but an abdication of medicine's obligation toserve the society in which it operates.
Franny Philos Sophia (Thu,) studied this question.